WARNING  This fixed-combination drug is not indicated for initial therapy of hypertension. Hypertension requires therapy titrated to the individual patient. If the fixed combination represents the dosage so determined, its use may be more convenient in patient management. The treatment of hypertension is not static but must be reevaluated as conditions in each patient warrant.

Hydralazine HCI and hydrochlorothiazide is an antihypertensive-diuretic combination available as capsules for oral administration. Hydralazine HCI and hydrochlorothiazide capsules of 25 mg /25 mg contain 25 mg of hydralazine hydrochloride USP and 25 mg of hydrochlorothiazide USP; capsules of 50 mg /50 mg contain 50 mg of hydralazine hydrochloride USP and 50 mg of hydrochlorothiazide USP; and capsules of 100 mg /50 mg contain 100 mg of hydralazine hydrochloride USP and 50 mg of hydrochlorothiazide USP.

Each tablet also contains the following inactive ingredients: Corn starch, crospovidone, gelatin, lactose monohydrate, pharmaceutical glaze, sodium starch glycolate, stearic acid, talc, and titanium dioxide. In addition, the 25 mg/25 mg capsule contains ammonium hydroxide, ethylene glycol monoethyl ether, propylene glycol and synthetic black iron oxide; the 50 mg/50 mg capsule contains FD&C Blue #1, FD&C Red #40, FD&C Yellow #6, synthetic red iron oxide and pharmaceutical shellac; and the 100 mg/50 mg capsule contains D&C Red #28, D&C Yellow #10, FD&C Blue #1, FD&C Blue #2, FD&C Red #40, propylene glycol and synthetic black iron oxide. Hydralazine hydrochloride is 1 hydrazinophthalazine monohydrochloride.

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. Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H -1,2.4-benzothiadiazine-7-sulfonamide 1 ,1 -dioxide. Chemical structure is as follows:

Hydrochlorothiazide USP is a white, or practically white, practically odorless crystalline powder. It is freely soluble in sodium hydroxide solution, in butylamine, and in dimethylformamide; sparingly soluble in methanol: slightly soluble in water: and insoluble in ether, in chloroform, and in dilute mineral acids. Its molecular weight is 297.75. Chemical structure is as follows:

Last updated on RxList: 12/8/2004

Hypertension (see boxed WARNING).

Dosage should be determined by individual titration (see boxed WARNING).

The usual dosage is one hydralazine HCl and hydrochlorothiazide capsule twice daily, the strength depending upon individual requirement following titration. For maintenance, the dosage should be adjusted to the lowest effective level.

When necessary, other antihypertensive agents such as sympathetic inhibitors may be added gradually in reduced dosages, and the effects should be watched carefully.

Hydralazine HCI and hydrochlorothiazide are supplied as two piece hard gelatin capsules, in three dosage strengths:

25 mg hydralazine hydrochloride and 25 mg hydrochlorothiazide capsules are white and imprinted "Par 143", and are available in bottles of 100 (NDC #49884-1 43-01) 500 (NDC #49884-1 43-05) and 1000 (NDC X49884-1 43-10).

50 mg hydralazine hydrochloride and 50 mg hydrochlorothiazide capsules are white/black and imprinted "Par 144", and are available in bottles of 100 (NDC X49884-144-01), 500 (NDC X49884-144-05) and 1000 (NDC #49884-144-10).

100 mg hydralazine hydrochloride and 50 mg hydrochlorothiazide capsules are powder blue/light blue and imprinted "Par 145", and are available in bottles of 100 (NDC #49884-1 45-01), 500 (NDC #49884-145-05) and 1000 (NDC #49884-145-10).

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

Dispense in a tight, light-resistant container as defined in the USP.

CAUTION: Federal law prohibits dispensing without prescription.

Last updated on RxList: 12/8/2004

Adverse reactions are usually reversible upon reduction of dosage or discontinuation of hydralazine HCI and hydrochlorothiazide. Whenever adverse reactions are moderate or severe, it may be necessary to discontinue the drug.

Hydralazine

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, and 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, and conjunctivitis.

Hydrochlorothiazide

The following adverse reactions have been observed but there has not been enough systematic collection of data to support an estimate of their frequency. Consequently the reactions are categorized by organ systems and are listed in decreasing order of severity and not frequency.

Digestive: Pancreatitis, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, anorexia.

Cardiovascular: Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics).

Neurologic: Vertigo, dizziness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness.

Musculoskeletal: Muscle spasm.

Hematologic: Aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia.

Metabolic: Hyperglycemia, glycosuria, and hyperuricemia.

Hypersensitive Reactions: Necrotizing angitis, Stevens-Johnson syndrome, respiratory distress including pneumonitis and pulmonary edema, purpura, urticaria, rash, photosensitivity.

Hydralazine

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 injections and hydralazine are used concomitantly.

Hydrochlorothiazide

Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).

Hypokalemia may develop during concomitant use of steroids or ACTH.

Insulin requirements in diabetic patients may be increased, decreased, or unchanged.

Thiazides may decrease arterial responsiveness to norepinephrine, but not enough to preclude effectiveness of the pressor agent for therapeutic use.

Thiazides may increase the responsiveness to tubocurarine.

Lithium renal clearance is reduced by thiazides, increasing the risk of lithium toxicity.

There have been rare reports in the literature of hemolytic anemia occurring with the concomitant use of hydrochlorothiazide and methyldopa.

Concurrent administration of some nonsteroidal anti-inflammatory agents may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics.

Drug/Laboratory Test Interactions

Thiazides may decrease serum levels of protein-bound iodine without signs of thyroid disturbance. Hydralazine HCI and hydrochlorothiazide should be discontinued before tests for parathyroid function are made (See General, Hydrochlorothiazide, Calcium excretion).

Last updated on RxList: 12/8/2004

Hydralazine

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. Signs and symptoms usually regress when the drug is discontinued, but residua have been detected many years later. Long-term treatment with steroids may be necessary.

Hydrochlorothiazide

Thiazides should be used with caution in patients with severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte imbalance may precipitate hepatic coma.

Thiazides may add to or potentiate the action of other antihypertensive drugs. Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.

Sensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma. The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.

General

Hydralazine: Myocardial stimulation produced by hydralazine can cause anginal attacks and ECG changes indicative of myocardial ischemia. The drug has been implicated in the production of myocardial infarction. It must, therefore, be used with caution in patients with suspected coronary artery disease.

The "hyperdynamic" circulation caused by hydralazine may accentuate specific cardiovascular inadequacies. For example, hydralazine may increase pulmonary artery pressure in patients with mitral valvular disease. The drug may reduce the pressor responses to epinephrine. Postural hypotension may result from hydralazine but is less common than with ganglionic blocking agents. It should be used with caution in patients with cerebral vascular accidents.

In hypertensive patients with normal kidneys who are treated with hydralazine, there is evidence of increased renal blood flow and a maintenance of glomerular filtration rate. In some instances where control values were below normal, improved renal function has been noted after administration of hydralazine. However, as with any antihypertensive agent, hydralazine should be used with caution in patients with advanced renal damage.

Peripheral neuritis, evidenced by paresthesia, numbness, and tingling, has been observed. Published evidence suggests that hydralazine has an antipyridoxine effect and that pyridoxine should be added to the regimen if symptoms develop.

Hydrochlorothiazide: All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance, namely hyponatremia, hypochloremic alkalosis, and hypokalemia (see Laboratory Tests and DRUG INTERACTIONS). Warning signs are dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbance, such as nausea or vomiting.

Hypokalemia may develop, especially in cases of brisk diuresis or severe cirrhosis.

Interference with adequate oral intake of electrolytes will also contribute to hypokalemia. Hypokalemia may be avoided or treated by the use of potassium supplements or foods with a high potassium content.

Any chloride deficit is generally mild and usually does not require specific treatment, except under extraordinary circumstances (as in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. In cases of actual salt depletion, appropriate replacement is the therapy of choice.

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

Latent diabetes may become manrtest during thiazide administration (see DRUG INTERACTIONS).

The antihypertensive effects of the drug may be enhanced in the postsympathectomy patient.

If progressive renal impairment becomes evident, withholding or discontinuing diuretic therapy should be considered.

Calcium excretion is decreased by thiazides. Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. The common complications of hyperparathyroidism, such as renal lithiasis, bone resorption and peptic ulceration, have not been seen.

Thiazide diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Laboratory Tests

Hydralazine: Complete blood counts and antinuclear antibody titer determinations are indicated before and periodically during prolonged therapy with hydralazine even though the patient is asymptomatic. These studies are also indicated if the patient develops arthralgia, fever, chest pain continued malaise, or other unexplained signs or symptoms. A positive antinuclear antibody titer requires that the physician carefully weigh the implications of the test results against the benefits to be derived from antihypertensive therapy with a combination drug containing hydralazine.

Blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, and purpura, have been reported. If such abnormalities develop, therapy should be discontinued.

Hydrochlorothiazide: Initial and periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids.

Carcinogenesis, Mutagenesis, impairment of Fertility

Carcinogenicity, mutagenicity, and fertility studies in animals have not been conducted with hydralazine HCl and hydrochlorothiazide.

Hydralazine: In a lifetime study in Swiss albino mice, there was a statistically significant increase in the incidence of lung tumors (adenomas and adenocarcinomas) of both male and female mice given hydralazine continuously in their drinking water at a dosage of about 250 mg/kg per day (about 80 times the maximum recommended human dose). In a 2-year carcinogenicity study of fats given hydralazine by gavage at doses o f 15,30, and 60 mg/k g per day (approximately 5 to 20 times the recommended human daily dose), microscopic examination of the liver revealed a small, but statistically significant, increase in benign neoplastic nodules in male and female rats from the high-dose group and in female rats from the intermediate-dose group. Benign interstitial cell tumors of the testes were also significantly increased in male rats from the high-dose group. The tumors observed are common in aged rats, and a significantly increased incidence was not observed until 18 months of treatment. Hydralazine was shown to be mutagenic in bacterial systems (Gene Mutation and DNA Repair) and in one of two rat and one rabbit hepatocyte in vitro DNA repair studies. Additional in vivo and in vitro studies using lymphoma cells, germinal cells, and fibroblasts from mice, bone marrow cells from Chinese hamsters and fibroblasts from human cell lines did not demonstrate any mutagenic potential for hydralazine.

The extent to which these findings indicate a risk to man is uncertain. While long-term clinical observation has not suggested that human cancer is associated with hydralazine use, epidemiologic studies have so far been insufficient to arrive at any conclusions.

Fertility studies in animals have not been conducted with hydralazine.

Hydrochlorothiazide: Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses up to approximately 600 mg/kg/da y or in male and female rats (at doses up to approximately 10 0 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in vitro assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (Ames assay) and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 130 0 ug/mL, and in the Aspergillus nidulans nondisjunction assay at an unspecified concentration.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses up to 100 and 4 mg/kg/day, respectively, prior to mating, and throughout gestation.

Pregnancy

Teratogenic Effects Pregnancy Category C

Animal reproduction studies have not been conducted with hydralazine HCI and hydrochlorothiazide.

Hydralazine: Animal studies indicate that hydralazine is teratogenic in mice at 20-30 times the maximum daily human dose of 200- 300 mg and possibly in rabbits a t 10-15 times the maximum daily human dose, but that it is nonteratogenic in rats. Teratogenic effects observed were cleft palate and malformations of facial and cranial bones.

Hydrochlorothiazide: Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 100 0 mg/kg/day, respectively, provided no evidence of harm to the fetus. There are, however, no adequate and well controlled studies of hydralazine HCI and hydrochlorothiazide in pregnant women. Because animal reproduction studies are not always predictive of human response, this combination drug should be used during pregnancy only it clearly needed

Nonteratogenic Effects

Hydrochlorothiazide: Thiazides cross the placental barrier and appear in cord blood, and there is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Nursing Mothers

It is not known whether hydralazine is excreted in human milk. Thiazides are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of the combination drug in children have not been established.

Last updated on RxList: 12/8/2004

Acute Toxicity

Oral LD50' s in rats (mg/kg): hydralazine, 173 and 187; hydrochlorothiazide, 2750.

Signs and Symptoms

Hydralazine: 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.

Hydrochlorothiazide: The most prominent feature of poisoning is acute loss of fluid and electrolytes.

Cardiovascular: Tachycardia, hypotension, and shock.

Neuromuscular: Weakness, confusion, dizziness, cramps of the calf muscles, paresthesia, fatigue, impairment of consciousness.

Digestive: Nausea, vomiting, thirst.

Renal: Polyuria, oliguria or anuria (due to hemoconcentration).

Laboratory Findings: Hypokalemia, hyponatremia, hypochloremia, alkalosis; increased BUN (especially in patients with renal insufficiency).

Combined Poisoning: Signs and symptoms may be aggravated or modified by concomitant intake of antihypertensive medication, barbiturates, curare, digitalis (hypokalemia), corticosteroids, narcotics, or alcohol.

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. Dialysis may not be effective for elimination of hydralazine HCI and hydrochlorothiazide because of its plasma protein binding (see CLINICAL PHARMACOLOGY).

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 in suspected hydralazine overdosage. Shock should be treated with plasma expanders. The patient's legs should be kept raised and lost fluid and electrolytes (potassium, sodium) should be replaced. 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.

Hydralazine

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

Hydrochlorothiazide

Anuria: hypersensitivity to this or other sulfonamide-derived drugs.

Last updated on RxList: 12/8/2004

Hydralazine

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.

Hydrochlorothiazide

Thiazides affect the renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage, all thiazides are approximately equal in their diuretic potency. Thiazides increase excretion of sodium and chloride in approximately equivalent amounts. Natriuresis causes a secondary loss of potassium. The mechanism of the antihypertensive effect of thiazides is unknown. Thiazides do not affect normal blood pressure.

Pharmacokinetics

Hydralazine: Hydralazine is rapidly absorbed after oral administration, and peak plasma levels are reached at l-2 hours. Plasma levels decline with a half-life of 3-7 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.

Administration of hydralazine with food results in higher levels of the drug in plasma.

Hydrochlorothiazide: Onset of action of thiazides occurs in 2 hours and the peak effect at about 4 hours. The action persists for approximately 6-12 hours. Hydrochlorothiazide is rapidly absorbed, as indicated by peak concentrations l-2.5 hours after oral administration. Plasma levels of the drug are proportional to dose; the concentration in whole blood is 1.6-l .8 times higher than in plasma. Thiazides are eliminated rapidly by the kidney. After oral administration of 25 to 100 mg doses, 72-97% of the dose is excreted in the urine, indicating dose-independent absorption. Hydrochlorothiazide is eliminated from plasma in a biphasic fashion with a terminal half-life of 10-l 7 hours. Plasma protein binding is 67.9%. Plasma clearance is 15.9-30.0 Uhr; volume of distribution is 3.6-7.8 L/kg.

Gastrointestinal absorption of hydrochlorothiazide is enhanced when administered with food. Absorption is decreased in patients with congestive heart failure, and the pharmacokinetics are considerably different in these patients.

Last updated on RxList: 12/8/2004

Patients should be informed of possible side effects and advised to take the medication regularly and continuously as directed.

Last updated on RxList: 12/8/2004

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

HYDRALAZINE/HYDROCHLOROTHIAZIDE - ORAL

(hye-DRAL-a-zeen/HYE-droe-KLOR-oh-THYE-a-zide)

COMMON BRAND NAME(S): Apresazide

WARNING: This product contains 2 drugs (hydralazine and hydrochlorothiazide). Generally, it should not be used when treating high blood pressure for the first time. Your doctor should first give you each of the drugs separately so that he or she can find the best dose of each drug for you. Use this combination product only if your doctor has decided that the doses of each drug in this product are right for your condition. Your doctor may need to continually adjust your medications depending on your condition.

USES: This medication contains 2 drugs (hydralazine and hydrochlorothiazide) and is used to treat high blood pressure. Hydralazine is called a vasodilator. It works by relaxing blood vessels so blood can flow through the body more easily. Hydrochlorothiazide is a "water pill" (diuretic). It works by increasing the amount of urine that you make. This effect causes your body to get rid of extra salt and water, which probably also helps relax the blood vessels. These 2 drugs are used together when 1 medication is not controlling your blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

HOW TO USE: Take this medication by mouth with or without food, usually twice daily or as directed by your doctor. It is best to avoid taking this medication within 4 hours of your bedtime to avoid having to get up to urinate. Consult your doctor or pharmacist if you have questions about your dosing schedule.

Cholestyramine and colestipol can decrease the absorption of this medication. If you are taking either of these drugs, take them at least 4 hours apart from this medication.

The dosage is based on your age, medical condition, and response to treatment. Your doctor may start you at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick. It may take up to several weeks before you get the full benefit of this drug.

Do not stop taking this medication without consulting your doctor. Some conditions may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.

Tell your doctor if your condition worsens (for example, your routine blood pressure readings increase).

SIDE EFFECTS: Headache, pounding/fast heartbeat, dizziness, loss of appetite, nausea, vomiting, diarrhea, or abdominal pain may occur as your body adjusts to the medication. You may also experience decreased sexual ability or increased sensitivity to the sun. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To reduce the risk of dizziness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may infrequently cause nerve problems. Tell your doctor promptly if you experience numbness or tingling. Your doctor may recommend a vitamin B6 supplement (pyridoxine).

Tell your doctor immediately if any of these unlikely but serious side effects occur: severe tiredness, aching/swollen joints, rash on nose and cheeks, swollen glands, change in the amount of urine, bloody/pink urine, dark urine, yellowing eyes/skin, signs of infection (such as fever, chills, persistent sore throat), easy bruising/bleeding.

The hydrochlorothiazide in this product may cause a loss of too much body water (dehydration) or salt/minerals. Tell your doctor immediately if you have any of these unlikely but serious symptoms of dehydration or salt/mineral loss: very dry mouth, thirst, muscle cramps/weakness, irregular heartbeat, unusual drowsiness, unusual decrease in the amount of urine, fainting, confusion, seizures.

Seek immediate medical attention if this rare but serious side effect occurs: chest/jaw/left arm pain.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking this product, tell your doctor or pharmacist if you are allergic to it; or to similar diuretics (such as chlorthalidone); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: inability to make urine (anuria), a certain heart condition (coronary heart disease), a certain heart valve problem (rheumatic heart disease of the mitral valve).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood vessel problems, kidney problems, liver problems, asthma, diabetes, lupus, gout, previous stroke, salt/mineral imbalance (such as imbalance of sodium/potassium/calcium/magnesium levels in the body), loss of too much body water (dehydration).

This drug may make you dizzy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

This medication may reduce the potassium levels in your blood. Ask your doctor about increasing the amount of potassium in your diet or about using a salt substitute that contains potassium. Your doctor may prescribe a potassium supplement.

If you have diabetes, this product may make it harder to control your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst/urination. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Before having surgery, tell your doctor or dentist that you are taking this medication.

Older adults may be more sensitive to the side effects of this medication, especially dizziness.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

This medication passes into breast milk. However, it is unlikely to harm a nursing infant. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: See also the How to Use section.

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: cisapride, dofetilide.

If you are currently using either of these medications, tell your doctor or pharmacist before starting this product.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: MAO inhibitors (isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, selegiline, tranylcypromine), corticosteroids (such as prednisone), lithium, nonsteroidal anti-inflammatory drugs-NSAIDs (such as ibuprofen, indomethacin).

Check the labels on all your medicines (such as cough-and-cold products, diet aids, pain relievers) because they may contain ingredients that could increase your blood pressure or heart rate. Ask your pharmacist about using those products safely.

This medication may interfere with certain laboratory tests (including amylase levels). Make sure laboratory personnel and your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting, flushing, chest/jaw/left arm pain, irregular heartbeat.

NOTES: Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise, and dietary changes may help this product work better. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Laboratory and/or medical tests (such as complete blood count, blood mineral levels) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Have your blood pressure checked regularly while taking this medication. Learn how to monitor your own blood pressure, and share the readings with your doctor.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised August 2008 Copyright(c) 2008 First DataBank, Inc.