Aldactazide

Potassium supplementation, either in the form of medication or as a diet rich in potassium, should not ordinarily be given in association with ALDACTAZIDE therapy. Excessive potassium intake may cause hyperkalemia in patients receiving ALDACTAZIDE (see PRECAUTIONS: General).

Concomitant administration of ALDACTAZIDE with the following drugs or potassium sources may lead to severe hyperkalemia:

• other potassium-sparing diuretics
• ACE inhibitors
• angiotensin II receptor antagonists
• aldosterone blockers
• non-steroidal anti-inflammatory drugs (NSAIDs), e.g., indomethacin
• heparin and low molecular weight heparin
• other drugs known to cause hyperkalemia
• potassium supplements
• diet rich in potassium
• salt substitutes containing potassium

ALDACTAZIDE should not be administered concurrently with other potassium-sparing diuretics. Spironolactone, when used with ACE inhibitors or indomethacin, even in the presence of a diuretic, has been associated with severe hyperkalemia. Extreme caution should be exercised when ALDACTAZIDE is given concomitantly with these drugs (see PRECAUTIONS: DRUG INTERACTIONS).

ALDACTAZIDE should be used with caution in patients with impaired hepatic function because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Lithium generally should not be given with diuretics (see PRECAUTIONS: DRUG INTERACTIONS).

Thiazides should be used with caution in 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 may add to or potentiate the action of other antihypertensive drugs.

Sensitivity reactions to thiazides may occur in patients with or without a history of allergy or bronchial asthma.

Sulfonamide derivatives, including thiazides, have been reported to exacerbate or activate systemic lupus erythematosus.

Acute Myopia And Secondary Angle-Closure Glaucoma

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Tell your doctor is you are breastfeeding or plan to breastfeed. 

Aldactazide's two ingredients, spironolactone and hydrochlorothiazide, have been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from Aldactazide, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered. 

• Take Aldactazide exactly as prescribed. 
• Aldactazide comes in a tablet form and is usually taken by mouth once daily with or without food. 

If you take too much Aldactazide, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away. 

Drinking alcohol can increase certain side effects of hydrochlorothiazide and spironolactone.

Do not use potassium supplements or salt substitutes while you are taking hydrochlorothiazide and spironolactone, unless your doctor has told you to.

Avoid a diet high in salt. Too much salt will cause your body to retain water and can make this medication less effective.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

In the U.S.

• Aldactazide

Available Dosage Forms:

• Tablet

Therapeutic Class: Diuretic, Potassium Sparing/Thiazide Combination

Pharmacologic Class: Diuretic, Potassium Sparing

Chemical Class: Thiazide

Use Aldactazide as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• Take with or without food. Take with food if it causes an upset stomach.
• This medicine may cause you to pass urine more often. To keep from having sleep problems, try to take before 6 pm.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Black, tarry, or bloody stools.
• Change in balance.
• Change in sex ability.
• Fever or chills.
• Sore throat.
• Throwing up blood or throw up that looks like coffee grounds.
• Slow heartbeat.
• A burning, numbness, or tingling feeling that is not normal.
• Shortness of breath.
• Any unexplained bruising or bleeding.
• For males, enlarged breasts.
• Period (menstrual) changes.
• This medicine can cause certain eye problems. If left untreated, this can lead to lasting eyesight loss. If eye problems happen, signs like change in eyesight or eye pain most often happen within hours to weeks of starting Aldactazide (hydrochlorothiazide and spironolactone). Call your doctor right away if you have these signs.

Mechanism of action

Aldactazide is a combination of two diuretic agents with different but complementary mechanisms and sites of action, thereby providing additive diuretic and antihypertensive effects. Additionally, the spironolactone component helps to minimize the potassium loss characteristically induced by the thiazide component.

The diuretic effect of spironolactone is mediated through its action as a specific pharmacologic antagonist of aldosterone, primarily by competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Hydrochlorothiazide promotes the excretion of sodium and water primarily by inhibiting their reabsorption in the cortical diluting segment of the distal renal tubule.

Aldactazide is effective in significantly lowering the systolic and diastolic blood pressure in many patients with essential hypertension, even when aldosterone secretion is within normal limits.

Both spironolactone and hydrochlorothiazide reduce exchangeable sodium, plasma volume, body weight, and blood pressure. The diuretic and antihypertensive effects of the individual components are potentiated when spironolactone and hydrochlorothiazide are given concurrently.

Pharmacokinetics

Spironolactone is rapidly and extensively metabolized. Sulfur-containing products are the predominant metabolites and are thought to be primarily responsible, together with spironolactone, for the therapeutic effects of the drug. The following pharmacokinetic data were obtained from 12 healthy volunteers following the administration of 100 mg of spironolactone (ALDACTONE film-coated tablets) daily for 15 days. On the 15th day, spironolactone was given immediately after a lowfat breakfast and blood was drawn thereafter.

The pharmacological activity of spironolactone metabolites in man is not known. However, in the adrenalectomized rat the antimineralocorticoid activities of the metabolites C, TMS, and HTMS, relative to spironolactone, were 1.10, 1.28, and 0.32, respectively. Relative to spironolactone, their binding affinities to the aldosterone receptors in rat kidney slices were 0.19, 0.86, and 0.06, respectively.

In humans, the potencies of TMS and 7-α-thiospirolactone in reversing the effects of the synthetic mineralocorticoid, fludrocortisone, on urinary electrolyte composition were 0.33 and 0.26, respectively, relative to spironolactone. However, since the serum concentrations of these steroids were not determined, their incomplete absorption and/or first-pass metabolism could not be ruled out as a reason for their reduced in vivo activities.

Spironolactone and its metabolites are more than 90% bound to plasma proteins. The metabolites are excreted primarily in the urine and secondarily in bile.

The effect of food on spironolactone absorption (two 100 mg ALDACTONE tablets) was assessed in a single dose study of 9 healthy, drug-free volunteers. Food increased the bioavailability of unmetabolized spironolactone by almost 100%. The clinical importance of this finding is not known.

Hydrochlorothiazide is rapidly absorbed following oral administration. Onset of action of hydrochlorothiazide is observed within one hour and persists for 6 to 12 hours. Hydrochlorothiazide plasma concentrations attain peak levels at one to two hours and decline with a half-life of four to five hours. Hydrochlorothiazide undergoes only slight metabolic alteration and is excreted in urine. It is distributed throughout the extracellular space, with essentially no tissue accumulation except in the kidney.

Spironolactone, an ingredient of Aldactazide, has been shown to be a tumorigen in chronic toxicity studies in rats (see Precautions section). Aldactazide should be used only in those conditions described below. Unnecessary use of this drug should be avoided.

Aldactazide is indicated for:

Edematous conditions for patients with:

Congestive heart failure:

• For the management of edema and sodium retention when the patient is only partially responsive to, or is intolerant of, other therapeutic measures;
• The treatment of diuretic-induced hypokalemia in patients with congestive heart failure when other measures are considered inappropriate;
• The treatment of patients with congestive heart failure taking digitalis when other therapies are considered inadequate or inappropriate.

Cirrhosis of the liver accompanied by edema and/or ascites:

• Aldosterone levels may be exceptionally high in this condition. Aldactazide is indicated for maintenance therapy together with bed rest and the restriction of fluid and sodium.

The nephrotic syndrome:

• For nephrotic patients when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics do not provide an adequate response.

Essential hypertension:

• For patients with essential hypertension in whom other measures are considered inadequate or inappropriate;
• In hypertensive patients for the treatment of a diuretic-induced hypokalemia when other measures are considered inappropriate;
• Aldactazide is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including the classes to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with Aldactazide.
  
  Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
  
  Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
  
  Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
  
  Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Usage in Pregnancy

The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developing toxemia.

Edema during pregnancy may arise from pathologic causes or from the physiologic and mechanical consequences of pregnancy. Aldactazide is indicated in pregnancy when edema is due to pathologic causes just as it is in the absence of pregnancy (however, see Precautions: Pregnancy). Dependent edema in pregnancy, resulting from restriction of venous return by the expanded uterus, is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is unsupported and unnecessary. There is hypervolemia during normal pregnancy which is not harmful to either the fetus or the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort that is not relieved by rest. In these cases, a short course of diuretics may provide relief and may be appropriate.