Apo-Hydralazine

Hydralazine hydrochloride.

Each tablet contains hydralazine 10 mg, 25 mg or 50 mg, respectively.

Various forms of hypertension: fixed essential hypertension, whether of benign or malignant character; hypertension associated with acute and chronic glomerulonephritis; nephrosclerosis; hypertensive toxemias of pregnancy, pre-eclampsia, and eclampsia.

Hypertension: In the ambulatory patient, initiate therapy in grdually increasing dosages; adjust according to individual response. Start with 10 mg 4 times daily for the first 2 to 4 days, increasing to 25 mg 4 times daily for balance of first week. For second and subsequent weeks, increase dosage to a maximum of 50 mg 4 times daily. For maintenance, adjust dosage to lowest effective levels. In combination with other hypotensive agents, lower dosages of hydralazine may be considered.

Symptoms: Hypotension and tachycardia.
Treatment: Gastric lavage or, in the absence of coma, emetics. In the presence of hypotension, cautiously give i.v. norepinephrine or ephedrine. General supportive measures include i.v. fluids, external heat, and elevation of foot on bed.

Hypersensitivity to hydralazine, coronary artery disease, mitral valvular rheumatic heart disease, acute dissecting aneurism of the aorta, lupus erythematosus, uremia.

Hydralazine may produce, in a few patients, a clinical picture simulating systematic lupus erythematosus. In such cases discontinue treatment immediately. Symptoms and signs usually regress when the drug is discontinued, but residual signs have been detected many years later. Long term treatment with adrenocorticosteroids may be necessary. Complete blood counts, L.E. cell preparations, and antinuclear antibody titer determinations are indicated before and periodically during prolonged therapy with hydralazine even though the patient is asymptomatic. These tests are also indicated if the patient develops arthralgia, fever, chest pain, continued malaise or other unexplained signs or symptoms. If the test results are abnormal, discontinue treatment.

Use cautiously in patients with coronary disease, advanced renal damage, and cerebrovascular accidents. In the rare patient with marked reduction of blood pressure, withdraw hydralazine gradually in order to avoid a possible sudden rise in pressure. In patients with more severe forms of hypertension and with uremia, too rapid an increase of dosage may produce a marked fall in blood pressure. In these cases, certain cerebral symptoms, from mild anxiety or depression to acute anxiety or severe depression and coma, may appear. Although hydralazine alone does not have a sedative or hypnotic effect, extreme drowsiness has occurred in patients taking it and a barbiturate. Similarly, the narcotic effect of alcohol has been potentiated by hydralazine. Periodic blood counts and liver function tests are advised during prolonged therapy.
Hydralazine HCl should not be used during the first trimester of pregnancy unless the potential benefits outweigh the possible risks.
Hydralazine is metabolized primarily by acetylation and dehydrazination. The rate of acetylation is genetically determined. Approximately 50% of Negroes and Caucasians are "slow inactivators"; the majority of Eskimos and Orientals are "rapid inactivators".
The rate of acetylation can significantly alter the effectiveness of hydralazine. Slow acetylation may lead to higher blood concentrations of the drug and, thus, to an increase in toxic reactions.

Hydralazine HCl should not be used during the first trimester of pregnancy unless the potential benefits outweigh the possible risks.
Animal studies indicate that high doses of hydralazine are teratogenic in mice, possibly in rabbits, but not in rats. 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 benefit clearly justifies the potential risk to the fetus. Hydralazine is excreted in human breast milk.

The more frequent early adverse effects (usually transitory) are: tachycardia, headache, palpitation, dizziness, weakness, nausea, vomiting, and postural hypotension. Less frequently numbness and tingling of the extremities, flushing, depression, nasal congestion, lacrimation, conjuctival injection, edema, tremors, dyspnea, skin rash, drug fever, muscle cramps, anginal symptoms, and giant urticaria. Adverse effects tend to disappear as treatment is continued. When they do not remit spontaneously or upon reduction of dosage, combination therapy with other agents such as reserpine or hydrochlorothiazide may be tried.
Peripheral neuritis, evidenced by paresthesias, numbness and tingling has been observed. Published evidence suggests an antipyridoxine effect and addition of pyridoxine to the regimen if symptoms develop.
Blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia, agranulocytosis and purpura have been reported rarely. If such abnormalities develop, discontinue therapy.
Late adverse effects: An arthritis-like syndrome has been observed in few a cases, usually after hydralazine was administered for long periods and in relatively high doses. The milder phase of the syndrome is characterized by migratory arthralgia in the joints of the hands and less commonly in the wrist, elbows, shoulders and knees. It may or may not be accompanied by fever. Continued use of hydralazine in these cases has been reported to lead to a clinical picture simulating acute systemic lupus erythematosus.
When early arthritis-like symptoms appear during therapy with hydralazine, spontaneous remission of symptoms usually follows withdrawal of the drug. The late reactions, which develop when treatment is continued despite the appearance of early symptoms, are more severe and longer lasting than the early phase. Most of these reactions have been completely reversible. Some patients may require protracted therapy, including ACTH and cortisone.

When hydralazine is administered with diuretics or other antihypertensive agents, the hypotensive effect of hydralazine may be increased. This effect is usually used to therapeutic advantage, but careful adjustment of dosage is necessary when these drugs are used concomitantly. Monoamine oxidase (MAO) inhibitors should be used with caution in patients receiving hydralazine since these drugs have a synergistic effect resulting in a marked decrease in blood pressure. Hydralazine may reduce the pressor response to epinephrine.
Indomethacin does not attenuate the effects of hydralazine in normal subjects, and thus does not support the hypothesis that endogenous prostaglandins are involved in the mechanism of action of hydralazine.

Store in tight light resistant containers. Protect from moisture, freezing and excessive heat.

Other Antihypertensives

C02DB02 - hydralazine ; Belongs to the class of hydrazinophthalazine derivatives. Used in the treatment of hypertension.

POM