Chlorthalidone is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

Chlorthalidone treats fluid retention (edema) in people with congestive heart failure, cirrhosis of the liver, or kidney disorders, or edema caused by taking steroids or estrogen.

Chlorthalidone is also used to treat high blood pressure (hypertension).

Chlorthalidone may also be used for purposes not listed in this medication guide.

Chlorthalidone side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Chlorthalidone may cause serious side effects. Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• low sodium–headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• low potassium–leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling;
• low magnesium–dizziness, irregular heartbeats, feeling jittery, muscle cramps, muscle spasms, cough or choking feeling; or
• kidney problems–little or no urination, swelling in your feet or ankles, feeling tired or short of breath.

Common side effects of chlorthalidone may include:

• low blood pressure (feeling light-headed);
• kidney problems;
• dizziness; or
• an electrolyte imbalance (such as low levels of potassium, sodium, or magnesium in your blood).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Warnings

You should not use chlorthalidone if you are unable to urinate, or if you are allergic to sulfa drugs.

Before taking this medicine

You should not use chlorthalidone if you are allergic to it, or if:

• you are unable to urinate; or
• you are allergic to sulfa drugs.

Tell your doctor if you have ever had:

• kidney disease;
• heart failure;
• gout;
• high cholesterol or triglycerides;
• diabetes; or
• if you are on a low-salt diet.

Tell your doctor if you are pregnant or plan to become pregnant. Taking chlorthalidone during pregnancy may cause side effects in the newborn baby, such as jaundice (yellowing of the skin or eyes), bruising or bleeding, low blood sugar, or an electrolyte imbalance.

Do not start or stop taking chlorthalidone during pregnancy without your doctor’s advice. Although chlorthalidone may cause side effects in a newborn, having high blood pressure during pregnancy can cause complications such as diabetes or eclampsia (dangerously high blood pressure that can lead to medical problems in both mother and baby). The benefit of treating hypertension may outweigh any risks to the baby.

You should not breastfeed while using chlorthalidone.

How should I take chlorthalidone?

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking chlorthalidone. This can lead to very low blood pressure, a serious electrolyte imbalance, or kidney failure.

Your blood pressure will need to be checked often. Your blood and urine may both be tested if you have been vomiting or are dehydrated.

chlorthalidone can affect the results of certain medical tests. Tell any doctor who treats you that you are using chlorthalidone.

If you need surgery, tell your surgeon you currently use this medicine.

If you have high blood pressure, keep using this medicine even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life.

Store this medicine at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Chlorthalidone dosing information

Usual Adult Dose for Hypertension:

-Initial dose: 25 mg orally once a day
-Titration: Increase to 50 mg orally once a day if response is inadequate; if response is still inadequate, increase to 100 mg orally once a day, or a second antihypertensive drug (step 2 therapy) may be added
-Maintenance dose: 25 to 100 mg orally once a day
-Maximum dose: 100 mg orally once a day

Comments:
-Doses should be taken in the morning with food.
-Maintenance doses may be lower than initial doses and should be adjusted according to individual patient response.
-Effectiveness is well sustained during continued use.

Use: Hypertension (alone or with another antihypertensive drug)

Usual Adult Dose for Edema:

-Initial dose: 50 to 100 mg orally once a day, or 100 mg orally every other day; some patients may require 150 to 200 mg orally at these intervals
-Maximum dose: 200 mg orally once a day

Comments:
-Doses should be taken in the morning with food.
-Maintenance doses may be lower than initial doses and should be adjusted according to individual patient response.
-Effectiveness is well sustained during continued use.

Use: For edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include nausea, weakness, dizziness, drowsiness, extreme thirst, muscle pain, or rapid heartbeats.

What should I avoid while taking chlorthalidone?

Drinking alcohol with chlorthalidone can cause side effects.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Avoid becoming overheated or dehydrated during exercise, in hot weather, or by not drinking enough fluids. Follow your doctor’s instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

What other drugs will affect chlorthalidone?

Using chlorthalidone with other drugs that make you light-headed can worsen this effect. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures.

Tell your doctor about all your other medicines, especially:

• other blood pressure medications;
• lithium;
• digoxin, digitalis;
• insulin or oral diabetes medicine; or
• steroid medicine.

Bumex ®(bumetanide) is a loop diuretic available as 0.5 mg (light green), 1 mg (yellow) and 2 mg (peach) tablets for oral administration; each tablet also contains anhydrous lactose, magnesium stearate, microcrystalline cellulose, pregelatinized starch and talc, with the following dye systems: 0.5 mg—D&C Yellow No. 10 aluminum lake and FD&C Blue No. 1 aluminum lake; 1 mg—D&C Yellow No. 10 aluminum lake; 2 mg—red iron oxide.

Chemically, bumetanide is 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid. It is a practically white powder having a calculated molecular weight of 364.42, and the following structural formula:

FDA-approved impurity specifications differ from the USP.

Bumex – Clinical Pharmacology

Bumex is a loop diuretic with a rapid onset and short duration of action. Pharmacological and clinical studies have shown that 1 mg Bumex has a diuretic potency equivalent to approximately 40 mg furosemide. The major site of Bumex action is the ascending limb of the loop of Henle.

The mode of action has been determined through various clearance studies in both humans and experimental animals. Bumex inhibits sodium reabsorption in the ascending limb of the loop of Henle, as shown by marked reduction of free-water clearance (CH 2O) during hydration and tubular free-water reabsorption (T CH 2O) during hydropenia. Reabsorption of chloride in the ascending limb is also blocked by Bumex, and Bumex is somewhat more chloruretic than natriuretic.

Potassium excretion is also increased by Bumex, in a dose-related fashion.

Bumex may have an additional action in the proximal tubule. Since phosphate reabsorption takes place largely in the proximal tubule, phosphaturia during Bumex induced diuresis is indicative of this additional action. This is further supported by the reduction in the renal clearance of Bumex by probenecid, associated with diminution in the natriuretic response. This proximal tubular activity does not seem to be related to an inhibition of carbonic anhydrase. Bumex does not appear to have a noticeable action on the distal tubule.

Bumex decreases uric acid excretion and increases serum uric acid. Following oral administration of Bumex the onset of diuresis occurs in 30 to 60 minutes. Peak activity is reached between 1 and 2 hours. At usual doses (1 mg to 2 mg) diuresis is largely complete within 4 hours; with higher doses, the diuretic action lasts for 4 to 6 hours. Diuresis starts within minutes following an intravenous injection and reaches maximum levels within 15 to 30 minutes.

Several pharmacokinetic studies have shown that bumetanide, administered orally or parenterally, is eliminated rapidly in humans, with a half-life of between 1 and 1½ hours. Plasma protein-binding is in the range of 94% to 96%.

Oral administration of carbon-14 labeled Bumex to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Urinary and biliary metabolites identified in this study were formed by oxidation of the N-butyl side chain. Biliary excretion of Bumex amounted to only 2% of the administered dose.

Pediatric Pharmacology

Elimination of bumetanide appears to be considerably slower in neonatal patients compared with adults, possibly because of immature renal and hepatobiliary function in this population. Small pharmacokinetic studies of intravenous bumetanide in preterm and full-term neonates with respiratory disorders have reported an apparent half-life of approximately 6 hours, with a range up to 15 hours and a serum clearance ranging from 0.2 mL/min/kg to 1.1 mL/min/kg. In a population of neonates receiving bumetanide for volume overload, mean serum clearance rates were 2.2 mL/min/kg in patients less than 2 months of age and 3.8 mL/min/kg in patients aged 2 to 6 months. Mean serum half-life of bumetanide was 2.5 hours and 1.5 hours in patients aged less than 2 months and those aged 2 to 6 months, respectively. Elimination half-life decreased considerably during the first month of life, from a mean of approximately 6 hours at birth to approximately 2.4 hours at 1 month of age.

In preterm neonates, mean serum concentrations following a single 0.05 mg/kg dose ranged from 126 μg/L at 1 hour to 57 μg/L at 8 hours. In another study, mean serum concentrations following a single 0.05 mg/kg dose were 338 ng/mL at 30 minutes and 176 ng/mL after 4 hours. A single dose of 0.1 mg/kg produced mean serum levels of 314 ng/mL at 1 hour, and 195 ng/mL at 6 hours. Mean volume of distribution in neonates and infants has been reported to range from 0.26 L/kg to 0.39 L/kg.

The degree of protein binding of bumetanide in cord sera from healthy neonates was approximately 97%, suggesting the potential for bilirubin displacement. A study using pooled sera from critically ill neonates found that bumetanide at concentrations of 0.5 μg/mL to 50 μg/mL, but not 0.25 μg/mL, caused a linear increase in unbound bilirubin concentrations.

In 56 infants aged 4 days to 6 months, bumetanide doses ranging from 0.005 mg/kg to 0.1 mg/kg were studied for pharmacodynamic effect. Peak bumetanide excretion rates increased linearly with increasing doses of drug. Maximal diuretic effect was observed at a bumetanide excretion rate of about 7 μg/kg/h, corresponding to doses of 0.035 mg/kg to 0.040 mg/kg. Higher doses produced a higher bumetanide excretion rate but no increase in diuretic effect. Urine flow rate peaked during the first hour after drug administration in 80% of patients and by 3 hours in all patients.

Geriatric Pharmacology

In a group of ten geriatric subjects between the ages of 65 and 73 years, total bumetanide clearance was significantly lower (1.8 ± 0.3 mL/min·kg) compared with younger subjects (2.9 ± 0.2 mL/min·kg) after a single oral bumetanide 0.5 mg dose. Maximum plasma concentrations were higher in geriatric subjects (16.9 ± 1.8 ng/mL) compared with younger subjects (10.3 ± 1.5 ng/mL). Urine flow rate and total excretion of sodium and potassium were increased less in the geriatric subjects compared with younger subjects, although potassium excretion and fractional sodium excretion were similar between the two age groups. Nonrenal clearance, bioavailability, and volume of distribution were not significantly different between the two groups.

Indications and Usage for Bumex

Bumex tablets are indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome.

Almost equal diuretic response occurs after oral and parenteral administration of bumetanide. Therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route.

Successful treatment with Bumex tablets following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity.

Contraindications

Bumex is contraindicated in anuria. Although Bumex can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or creatinine, or the development of oliguria during therapy of patients with progressive renal disease, is an indication for discontinuation of treatment with Bumex. Bumex is also contraindicated in patients in hepatic coma or in states of severe electrolyte depletion until the condition is improved or corrected. Bumex is contraindicated in patients hypersensitive to this drug.

Warnings

Volume and Electrolyte Depletion

The dose of Bumex should be adjusted to the patient’s need. Excessive doses or too frequent administration can lead to profound water loss, electrolyte depletion, dehydration, reduction in blood volume and circulatory collapse with the possibility of vascular thrombosis and embolism, particularly in elderly patients.

Hypokalemia

Hypokalemia can occur as a consequence of Bumex administration. Prevention of hypokalemia requires particular attention in the following conditions: patients receiving digitalis and diuretics for congestive heart failure, hepatic cirrhosis and ascites, states of aldosterone excess with normal renal function, potassium-losing nephropathy, certain diarrheal states, or other states where hypokalemia is thought to represent particular added risks to the patient, i.e., history of ventricular arrhythmias.

In patients with hepatic cirrhosis and ascites, sudden alterations of electrolyte balance may precipitate hepatic encephalopathy and coma. Treatment in such patients is best initiated in the hospital with small doses and careful monitoring of the patient’s clinical status and electrolyte balance. Supplemental potassium and/or spironolactone may prevent hypokalemia and metabolic alkalosis in these patients.

Ototoxicity

In cats, dogs and guinea pigs, bumetanide has been shown to produce ototoxicity. In these test animals bumetanide was 5 to 6 times more potent than furosemide and, since the diuretic potency of bumetanide is about 40 to 60 times furosemide, it is anticipated that blood levels necessary to produce ototoxicity will rarely be achieved. The potential exists, however, and must be considered a risk of intravenous therapy, especially at high doses, repeated frequently in the face of renal excretory function impairment. Potentiation of aminoglycoside ototoxicity has not been tested for bumetanide. Like other members of this class of diuretics, bumetanide probably shares this risk.

Allergy to Sulfonamides

Patients allergic to sulfonamides may show hypersensitivity to Bumex.

Thrombocytopenia

Since there have been rare spontaneous reports of thrombocytopenia from postmarketing experience, patients should be observed regularly for possible occurrence of thrombocytopenia.

Precautions

General

Serum potassium should be measured periodically and potassium supplements or potassium sparing diuretics added if necessary. Periodic determinations of other electrolytes are advised in patients treated with high doses or for prolonged periods, particularly in those on low-salt diets.

Hyperuricemia may occur; it has been asymptomatic in cases reported to date. Reversible elevations of the BUN and creatinine may also occur, especially in association with dehydration and particularly in patients with renal insufficiency. Bumex may increase urinary calcium excretion with resultant hypocalcemia.

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

Laboratory Tests

Studies in normal subjects receiving Bumex revealed no adverse effects on glucose tolerance, plasma insulin, glucagon and growth hormone levels, but the possibility of an effect on glucose metabolism exists. Periodic determinations of blood sugar should be done, particularly in patients with diabetes or suspected latent diabetes.

Patients under treatment should be observed regularly for possible occurrence of blood dyscrasias, liver damage or idiosyncratic reactions, which have been reported occasionally in foreign marketing experience. The relationship of these occurrences to Bumex use is not certain.

Drug Interactions

Drugs with Ototoxic Potential 

Especially in the presence of impaired renal function, the use of parenterally administered bumetanide in patients to whom aminoglycoside antibiotics are also being given should be avoided, except in life-threatening conditions.

Drugs with Nephrotoxic Potential

There has been no experience with the concurrent use of Bumex with drugs known to have a nephrotoxic potential. Therefore, the simultaneous administration of these drugs should be avoided.

Lithium

Lithium should generally not be given with diuretics (such as Bumex) because they reduce its renal clearance and add a high risk of lithium toxicity.

Probenecid

Pretreatment with probenecid reduces both the natriuresis and hyperreninemia produced by Bumex. This antagonistic effect of probenecid on Bumex natriuresis is not due to a direct action on sodium excretion but is probably secondary to its inhibitory effect on renal tubular secretion of bumetanide. Thus, probenecid should not be administered concurrently with Bumex.

Indomethacin

Indomethacin blunts the increases in urine volume and sodium excretion seen during Bumex treatment and inhibits the bumetanide-induced increase in plasma renin activity. Concurrent therapy with Bumex is thus not recommended.

Antihypertensives

Bumex may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs.

Digoxin

Interaction studies in humans have shown no effect on digoxin blood levels.

Anticoagulants

Interaction studies in humans have shown Bumex to have no effect on warfarin metabolism or on plasma prothrombin activity.

Carcinogenesis, Mutagenesis and Impairment of Fertility

Bumex was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitrometabolic activation system. An 18-month study showed an increase in mammary adenomas of questionable significance in female rats receiving oral doses of 60 mg/kg/day (2000 times a 2-mg human dose). A repeat study at the same doses failed to duplicate this finding.

Reproduction studies were performed to evaluate general reproductive performance and fertility in rats at oral dose levels of 10, 30, 60 or 100 mg/kg/day. The pregnancy rate was slightly decreased in the treated animals; however, the differences were small and not statistically significant.

Pregnancy

Teratogenic Effects

Bumex is neither teratogenic nor embryocidal in mice when given in doses up to 3400 times the maximum human therapeutic dose.

Bumex has been shown to be nonteratogenic, but it has a slight embryocidal effect in rats when given in doses of 3400 times the maximum human therapeutic dose and in rabbits at doses of 3.4 times the maximum human therapeutic dose. In one study, moderate growth retardation and increased incidence of delayed ossification of sternebrae were observed in rats at oral doses of 100 mg/kg/day, 3400 times the maximum human therapeutic dose. These effects were associated with maternal weight reductions noted during dosing. No such adverse effects were observed at 30 mg/kg/day (1000 times the maximum human therapeutic dose). No fetotoxicity was observed at 1000 to 2000 times the human therapeutic dose.

In rabbits, a dose-related decrease in litter size and an increase in resorption rate were noted at oral doses of 0.1 mg/kg/day and 0.3 mg/kg/day (3.4 and 10 times the maximum human therapeutic dose). A slightly increased incidence of delayed ossification of sternebrae occurred at 0.3 mg/kg/day; however, no such adverse effects were observed at the dose of 0.03 mg/kg/day. The sensitivity of the rabbit to Bumex parallels the marked pharmacologic and toxicologic effects of the drug in this species.

Bumex was not teratogenic in the hamster at an oral dose of 0.5 mg/kg/day (17 times the maximum human therapeutic dose). Bumetanide was not teratogenic when given intravenously to mice and rats at doses up to 140 times the maximum human therapeutic dose.

There are no adequate and well-controlled studies in pregnant women. A small investigational experience in the and marketing experience in other countries to date have not indicated any evidence of adverse effects on the fetus, but these data do not rule out the possibility of harmful effects. Bumex should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while the patient is on Bumex since it may be excreted in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 have not been established.

In vitrostudies using pooled sera from critically ill neonates have shown bumetanide to be a potent displacer of bilirubin . The administration of bumetanide could present a particular concern if given to critically ill or jaundiced neonates at risk for kernicterus.

Geriatric Use

Clinical studies of Bumex did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Adverse Reactions/Side Effects

The most frequent clinical adverse reactions considered probably or possibly related to Bumex are muscle cramps (seen in 1.1% of treated patients), dizziness (1.1%), hypotension (0.8%), headache (0.6%), nausea (0.6%) and encephalopathy (in patients with pre-existing liver disease) (0.6%). One or more of these adverse reactions have been reported in approximately 4.1% of patients treated with Bumex.

Serious skin reactions (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported in association with bumetanide use.

Less frequent clinical adverse reactions to Bumex are impaired hearing (0.5%), pruritus (0.4%), electrocardiogram changes (0.4%), weakness (0.2%), hives (0.2%), abdominal pain (0.2%), arthritic pain (0.2%), musculoskeletal pain (0.2%), rash (0.2%) and vomiting (0.2%). One or more of these adverse reactions have been reported in approximately 2.9% of patients treated with Bumex.

Other clinical adverse reactions, which have each occurred in approximately 0.1% of patients, are vertigo, chest pain, ear discomfort, fatigue, dehydration, sweating, hyperventilation, dry mouth, upset stomach, renal failure, asterixis, itching, nipple tenderness, diarrhea, premature ejaculation and difficulty maintaining an erection.

Laboratory abnormalities reported have included hyperuricemia (in 18.4% of patients tested), hypochloremia (14.9%), hypokalemia (14.7%), azotemia (10.6%), hyponatremia (9.2%), increased serum creatinine (7.4%), hyperglycemia (6.6%), and variations in phosphorus (4.5%), CO content (4.3%), bicarbonate (3.1%) and calcium (2.4%). Although manifestations of the pharmacologic action of Bumex, these conditions may become more pronounced by intensive therapy.

Also reported have been thrombocytopenia (0.2%) and deviations in hemoglobin (0.8%), prothrombin time (0.8%), hematocrit (0.6%), WBC (0.3%) and differential counts (0.1%). There have been rare spontaneous reports of thrombocytopenia from postmarketing experience.

Diuresis induced by Bumex may also rarely be accompanied by changes in LDH (1.0%), total serum bilirubin (0.8%), serum proteins (0.7%), SGOT (0.6%), SGPT (0.5%), alkaline phosphatase (0.4%), cholesterol (0.4%) and creatinine clearance (0.3%). Increases in urinary glucose (0.7%) and urinary protein (0.3%) have also been seen.

Overdosage

Overdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.

Bumex Dosage and Administration

Individualize dosage with careful monitoring of patient response.

Oral Administration

The usual total daily dosage of Bumex tablets is 0.5 mg to 2 mg and in most patients is given as a single dose.

If the diuretic response to an initial dose of Bumex tablets is not adequate, in view of its rapid onset and short duration of action, a second or third dose may be given at 4- to 5-hour intervals up to a maximum daily dose of 10 mg. An intermittent dose schedule, whereby Bumex tablets are given on alternate days or for 3 to 4 days with rest periods of 1 to 2 days in between, is recommended as the safest and most effective method for the continued control of edema. In patients with hepatic failure, keep the dosage to a minimum.

Because cross-sensitivity with furosemide has rarely been observed, bumetanide can be substituted at approximately a 1:40 ratio of bumetanide in proportion to furosemide in patients allergic to furosemide.

Parenteral Administration

Bumetanide injection may be administered parenterally (intravenously and intramuscularly) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical.

Terminate parenteral treatment and institute oral treatment as soon as possible.

How is Bumex supplied

Bumex Tablets for oral administration are elliptical, flat-faced, and bevel-edged, available as:

Store at 68° to 77°F (20° to 25°C); excursions permitted between 59° to 86°F (15° to 30°C) [See USP Controlled Room Temperature].

Dispense contents in a tight, light-resistant container as defined in the USP with a child-resistant closure, as required.

Manufactured for andDistributed by:
Validus Pharmaceuticals LLC
Parsippany, NJ 07054
info@validuspharma.com
www.validuspharma.com
1-866-982-5438

Product of Italy

© 2023 Validus Pharmaceuticals LLC

60018-05 November 2023

PRINCIPAL DISPLAY PANEL

NDC 30698-630-01
Bumex ®
(bumetanide) Tablets
0.5 mg
100 Tablets
Rx Only

PRINCIPAL DISPLAY PANEL

NDC 30698-631-01
Bumex ®
(bumetanide) Tablets
1 mg
100 Tablets
Rx Only

NDC 30698-631-05
Bumex ®
(bumetanide) Tablets
1 mg
500 Tablets
Rx Only

PRINCIPAL DISPLAY PANEL

NDC 30698-632-01
Bumex ®
(bumetanide) Tablets
2 mg
100 Tablets
Rx Only

NDC 30698-632-05
Bumex ®
(bumetanide) Tablets
2 mg
500 Tablets
Rx Only

Bumetanide is a loop diuretic, available as 4 mL vials and 10 mL vials (0.25 mg/mL) for intravenous or intramuscular injection as a sterile solution.

Each mL contains 0.25 mg bumetanide compounded with 0.85% sodium chloride and 0.4% ammonium acetate as buffers; 0.01% edetate disodium; 1% benzyl alcohol as preservative in water for injection and pH adjusted to 6.8 to 7.8 with sodium hydroxide.

Chemically, bumetanide is 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid. It is a practically white or almost white, crystalline powder having a calculated molecular weight of 364.42, and the following structural formula:

Bumetanide – Clinical Pharmacology

Bumetanide is a loop diuretic with a rapid onset and short duration of action. Pharmacological and clinical studies have shown that 1 mg bumetanide has a diuretic potency equivalent to approximately 40 mg furosemide. The major site of bumetanide action is the ascending limb of the loop of Henle.

The mode of action has been determined through various clearance studies in both humans and experimental animals. Bumetanide inhibits sodium reabsorption in the ascending limb of the loop of Henle, as shown by marked reduction of free-water clearance (CH2O) during hydration and tubular free-water reabsorption (TcH2O) during hydropenia. Reabsorption of chloride in the ascending limb is also blocked by bumetanide, and bumetanide is somewhat more chloruretic than natriuretic.

Potassium excretion is also increased by bumetanide, in a dose-related fashion.

Bumetanide may have an additional action in the proximal tubule. Since phosphate reabsorption takes place largely in the proximal tubule, phosphaturia during bumetanide induced diuresis is indicative of this additional action. This is further supported by the reduction in the renal clearance of bumetanide by probenecid, associated with diminution in the natriuretic response. This proximal tubular activity does not seem to be related to an inhibition of carbonic anhydrase. Bumetanide does not appear to have a noticeable action on the distal tubule.

Bumetanide decreases uric acid excretion and increases serum uric acid. Diuresis starts within minutes following an intravenous injection and reaches maximum levels within 15 to 30 minutes.

Several pharmacokinetic studies have shown that bumetanide, administered orally or parenterally, is eliminated rapidly in humans, with a half-life of between 1 and 1½ hours. Plasma protein-binding is in the range of 94% to 96%.

Oral administration of carbon-14 labeled bumetanide to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Urinary and biliary metabolites identified in this study were formed by oxidation of the N-butyl side chain. Biliary excretion of bumetanide amounted to only 2% of the administered dose.

Pediatric Pharmacology

Elimination of bumetanide appears to be considerably slower in neonatal patients compared with adults, possibly because of immature renal and hepatobiliary function in this population. Small pharmacokinetic studies of intravenous bumetanide in preterm and full-term neonates with respiratory disorders have reported an apparent half-life of approximately 6 hours, with a range up to 15 hours and a serum clearance ranging from 0.2 to 1.1 mL/min/kg. In a population of neonates receiving bumetanide for volume overload, mean serum clearance rates were 2.17 mL/min/kg in patients less than 2 months of age and 3.8 mL/min/kg in patients aged 2 to 6 months. Mean serum half-life of bumetanide was 2.5 hours and 1.5 hours in patients aged less than 2 months and those aged 2 to 6 months, respectively. Elimination half-life decreased considerably during the first month of life, from a mean of approximately 6 hours at birth to approximately 2.4 hours at 1 month of age.

In preterm neonates, mean serum concentrations following a single 0.05 mg/kg dose ranged from 126 mcg/L at 1 hour to 57 mcg/L at 8 hours. In another study, mean serum concentrations following a single 0.05 mg/kg dose were 338 ng/mL at 30 minutes and 176 ng/mL after 4 hours. A single dose of 0.1 mg/kg produced mean serum levels of 314 ng/mL at 1 hour, and 195 ng/mL at 6 hours. Mean volume of distribution in neonates and infants has been reported to range from 0.26 L/kg to 0.39 L/kg.

The degree of protein binding of bumetanide in cord sera from healthy neonates was approximately 97%, suggesting the potential for bilirubin displacement. A study using pooled sera from critically ill neonates found that bumetanide at concentrations of 0.5 to 50 mcg/mL, but not 0.25 mcg/mL, caused a linear increase in unbound bilirubin concentrations.

In 56 infants aged 4 days to 6 months, bumetanide doses ranging from 0.005 mg/kg to 0.1 mg/kg were studied for pharmacodynamic effect. Peak bumetanide excretion rates increased linearly with increasing doses of drug. Maximal diuretic effect was observed at a bumetanide excretion rate of about 7 mcg/kg/hr, corresponding to doses of 0.035 to 0.040 mg/kg. Higher doses produced a higher bumetanide excretion rate but no increase in diuretic effect. Urine flow rate peaked during the first hour after drug administration in 80% of patients and by 3 hours in all patients.

Geriatric Pharmacology

In a group of ten geriatric subjects between the ages of 65 and 73 years, total bumetanide clearance was significantly lower (1.8 ± 0.3 mL/min/kg) compared with younger subjects

(2.9 ± 0.2 mL/min/kg) after a single oral bumetanide 0.5 mg dose. Maximum plasma concentrations were higher in geriatric subjects (16.9 ± 1.8 ng/mL) compared with younger subjects (10.3 ± 1.5 ng/mL). Urine flow rate and total excretion of sodium and potassium were increased less in the geriatric subjects compared with younger subjects, although potassium excretion and fractional sodium excretion were similar between the two age groups. Nonrenal clearance, bioavailability, and volume of distribution were not significantly different between the two groups.

Indications and Usage for Bumetanide

Bumetanide injection, USP is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome.

Almost equal diuretic response occurs after oral and parenteral administration of bumetanide. Therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route.

Successful treatment with bumetanide injection, USP following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity.

Contraindications

Bumetanide is contraindicated in anuria. Although bumetanide can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or creatinine, or the development of oliguria during therapy of patients with progressive renal disease, is an indication for discontinuation of treatment with bumetanide. Bumetanide is also contraindicated in patients in hepatic coma or in states of severe electrolyte depletion until the condition is improved or corrected. Bumetanide is contraindicated in patients hypersensitive to this drug.

Warnings

Volume and Electrolyte Depletion

The dose of bumetanide should be adjusted to the patient’s need. Excessive doses or too frequent administration can lead to profound water loss, electrolyte depletion, dehydration, reduction in blood volume and circulatory collapse with the possibility of vascular thrombosis and embolism, particularly in elderly patients.

Hypokalemia

Hypokalemia can occur as a consequence of bumetanide administration. Prevention of hypokalemia requires particular attention in the following conditions: patients receiving digitalis and diuretics for congestive heart failure, hepatic cirrhosis and ascites, states of aldosterone excess with normal renal function, potassium-losing nephropathy, certain diarrheal states, or other states where hypokalemia is thought to represent particular added risks to the patient, i.e., history of ventricular arrhythmias.

In patients with hepatic cirrhosis and ascites, sudden alterations of electrolyte balance may precipitate hepatic encephalopathy and coma. Treatment in such patients is best initiated in the hospital with small doses and careful monitoring of the patient’s clinical status and electrolyte balance. Supplemental potassium and/or spironolactone may prevent hypokalemia and metabolic alkalosis in these patients.

Ototoxicity

In cats, dogs and guinea pigs, bumetanide has been shown to produce ototoxicity. In these test animals, bumetanide was 5 to 6 times more potent than furosemide and, since the diuretic potency of bumetanide is about 40 to 60 times furosemide, it is anticipated that blood levels necessary to produce ototoxicity will rarely be achieved. The potential exists, however, and must be considered a risk of intravenous therapy, especially at high doses, repeated frequently in the face of renal excretory function impairment. Potentiation of aminoglycoside ototoxicity has not been tested for bumetanide. Like other members of this class of diuretics, bumetanide probably shares this risk.

Allergy to Sulfonamides

Patients allergic to sulfonamides may show hypersensitivity to bumetanide.

Thrombocytopenia

Since there have been rare spontaneous reports of thrombocytopenia from postmarketing experience, patients should be observed regularly for possible occurrence of thrombocytopenia.

Precautions

General

Serum potassium should be measured periodically and potassium supplements or potassium-sparing diuretics added if necessary. Periodic determinations of other electrolytes are advised in patients treated with high doses or for prolonged periods, particularly in those on low-salt diets.

Hyperuricemia may occur; it has been asymptomatic in cases reported to date. Reversible elevations of the BUN and creatinine may also occur, especially in association with dehydration and particularly in patients with renal insufficiency. Bumetanide may increase urinary calcium excretion with resultant hypocalcemia.

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

Laboratory Tests

Studies in normal subjects receiving bumetanide revealed no adverse effects on glucose tolerance, plasma insulin, glucagon and growth hormone levels, but the possibility of an effect on glucose metabolism exists. Periodic determinations of blood sugar should be done, particularly in patients with diabetes or suspected latent diabetes.

Patients under treatment should be observed regularly for possible occurrence of blood dyscrasias, liver damage or idiosyncratic reactions, which have been reported occasionally in foreign marketing experience. The relationship of these occurrences to bumetanide use is not certain.

Drug Interactions

Drugs with Ototoxic Potential

Especially in the presence of impaired renal function, the use of parenterally administered bumetanide in patients to whom aminoglycoside antibiotics are also being given should be avoided, except in life-threatening conditions.

Drugs with Nephrotoxic Potential

There has been no experience with the concurrent use of bumetanide with drugs known to have a nephrotoxic potential. Therefore, the simultaneous administration of these drugs should be avoided.

Lithium

Lithium should generally not be given with diuretics (such as bumetanide) because they reduce its renal clearance and add a high risk of lithium toxicity.

Probenecid

Pretreatment with probenecid reduces both the natriuresis and hyperreninemia produced by bumetanide. This antagonistic effect of probenecid on bumetanide natriuresis is not due to a direct action on sodium excretion but is probably secondary to its inhibitory effect on renal tubular secretion of bumetanide. Thus, probenecid should not be administered concurrently with bumetanide.

Indomethacin

Indomethacin blunts the increases in urine volume and sodium excretion seen during bumetanide treatment and inhibits the bumetanide-induced increase in plasma renin activity. Concurrent therapy with bumetanide is thus not recommended.

Antihypertensives

Bumetanide may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs.

Digoxin

Interaction studies in humans have shown no effect on digoxin blood levels.

Anticoagulants

Interaction studies in humans have shown bumetanide to have no effect on warfarin metabolism or on plasma prothrombin activity.

Carcinogenesis, Mutagenesis and Impairment of Fertility

Bumetanide was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitro metabolic activation system. An 18-month study showed an increase in mammary adenomas of questionable significance in female rats receiving oral doses of 60 mg/kg/day (2000 times a 2-mg human dose). A repeat study at the same doses failed to duplicate this finding.

Reproduction studies were performed to evaluate general reproductive performance and fertility in rats at oral dose levels of 10, 30, 60 or 100 mg/kg/day. The pregnancy rate was slightly decreased in the treated animals; however, the differences were small and not statistically significant.

Pregnancy

Teratogenic Effects

Bumetanide is neither teratogenic nor embryocidal in mice when given in doses up to 3400 times the maximum human therapeutic dose.

Bumetanide has been shown to be nonteratogenic, but it has a slight embryocidal effect in rats when given in doses of 3400 times the maximum human therapeutic dose and in rabbits at doses of 3.4 times the maximum human therapeutic dose. In one study, moderate growth retardation and increased incidence of delayed ossification of sternebrae were observed in rats at oral doses of 100 mg/kg/day, 3400 times the maximum human therapeutic dose. These effects were associated with maternal weight reductions noted during dosing. No such adverse effects were observed at 30 mg/kg/day (1000 times the maximum human therapeutic dose). No fetotoxicity was observed at 1000 to 2000 times the human therapeutic dose.

In rabbits, a dose-related decrease in litter size and an increase in resorption rate were noted at oral doses of 0.1 and 0.3 mg/kg/day (3.4 and 10 times the maximum human therapeutic dose). A slightly increased incidence of delayed ossification of sternebrae occurred at 0.3 mg/kg/day; however, no such adverse effects were observed at the dose of 0.03 mg/kg/day. The sensitivity of the rabbit to bumetanide parallels the marked pharmacologic and toxicologic effects of the drug in this species.

Bumetanide was not teratogenic in the hamster at an oral dose of 0.5 mg/kg/day (17 times the maximum human therapeutic dose). Bumetanide was not teratogenic when given intravenously to mice and rats at doses up to 140 times the maximum human therapeutic dose.

There are no adequate and well-controlled studies in pregnant women. A small investigational experience in the United States and marketing experience in other countries to date have not indicated any evidence of adverse effects on the fetus, but these data do not rule out the possibility of harmful effects. Bumetanide should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while the patient is on bumetanide since it may be excreted in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 have not been established.

In vitro studies using pooled sera from critically ill neonates have shown bumetanide to be a potent displacer of bilirubin [see Clinical Pharmacology: Pediatric Pharmacology]. The administration of bumetanide could present a particular concern if given to critically ill or jaundiced neonates at risk for kernicterus.

Geriatric Use

Clinical studies of bumetanide did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Adverse Reactions/Side Effects

The most frequent clinical adverse reactions considered probably or possibly related to bumetanide are muscle cramps (seen in 1.1% of treated patients), dizziness (1.1%), hypotension (0.8%), headache (0.6%), nausea (0.6%) and encephalopathy (in patients with preexisting liver disease) (0.6%). One or more of these adverse reactions have been reported in approximately 4.1% of patients treated with bumetanide.

Less frequent clinical adverse reactions to bumetanide are impaired hearing (0.5%), pruritus (0.4%), electrocardiogram changes (0.4%), weakness (0.2%), hives (0.2%), abdominal pain (0.2%), arthritic pain (0.2%), musculoskeletal pain (0.2%), rash (0.2%) and vomiting (0.2%). One or more of these adverse reactions have been reported in approximately 2.9% of patients treated with bumetanide.

Other clinical adverse reactions, which have each occurred in approximately 0.1% of patients, are vertigo, chest pain, ear discomfort, fatigue, dehydration, sweating, hyperventilation, dry mouth, upset stomach, renal failure, asterixis, itching, nipple tenderness, diarrhea, premature ejaculation and difficulty maintaining an erection.

Laboratory abnormalities reported have included hyperuricemia (in 18.4% of patients tested), hypochloremia (14.9%), hypokalemia (14.7%), azotemia (10.6%), hyponatremia (9.2%), increased serum creatinine (7.4%), hyperglycemia (6.6%), and variations in phosphorus (4.5%), CO2 content (4.3%), bicarbonate (3.1%) and calcium (2.4%). Although manifestations of the pharmacologic action of bumetanide, these conditions may become more pronounced by intensive therapy.

Also reported have been thrombocytopenia (0.2%) and deviations in hemoglobin (0.8%), prothrombin time (0.8%), hematocrit (0.6%), WBC (0.3%) and differential counts (0.1%). There have been rare spontaneous reports of thrombocytopenia from postmarketing experience.

Diuresis induced by bumetanide may also rarely be accompanied by changes in LDH (1.0%), total serum bilirubin (0.8%), serum proteins (0.7%), SGOT (0.6%), SGPT (0.5%), alkaline phosphatase (0.4%), cholesterol (0.4%) and creatinine clearance (0.3%). Increases in urinary glucose (0.7%) and urinary protein (0.3%) have also been seen.

Overdosage

Overdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.

Bumetanide Dosage and Administration

Dosage should be individualized with careful monitoring of patient response.

Parenteral Administration

Bumetanide Injection may be administered parenterally (IV or IM) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical.

Parenteral treatment should be terminated and oral treatment instituted as soon as possible.

The usual initial dose is 0.5 mg to 1 mg intravenously or intramuscularly. Intravenous administration should be given over a period of 1 to 2 minutes. If the response to an initial dose is deemed insufficient, a second or third dose may be given at intervals of 2 to 3 hours, but should not exceed a daily dosage of 10 mg.

Miscibility and Parenteral Solutions

The compatibility tests of bumetanide injection with 5% dextrose in water, 0.9% sodium chloride and lactated Ringer’s solution in both glass and plasticized PVC (Viaflex) containers have shown no significant absorption effect with either containers, nor a measurable loss of potency due to degradation of the drug. However, solutions should be freshly prepared and used within 24 hours.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

How is Bumetanide supplied

Bumetanide Injection USP, 0.25 mg/mL is a sterile, clear, colorless to slightly yellow solution free from visible particulate matter supplied in amber vials as follows:

4 mL Single Dose Vial packaged in 10s (NDC 70748-323-10)

Discard unused portion.

10 mL Multiple Dose Vial packaged in 10s (NDC 70748-323-11)

This container closure is not made with natural rubber latex.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30° C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from light.

To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Naples, FL 34108

United States

Manufactured by:

Lupin Limited

Nagpur – 441108

India

Revised: November 2024 #ID: 278600

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Bumetanide Injection, USP

1 mg/4 mL (0.25 mg/mL)

4 mL Single Dose Vial

NDC 70748-323-01

Bumetanide Injection, USP

1 mg/4 mL (0.25 mg/mL)

10 x 4 mL Single Dose Vials

NDC 70748-323-10

Bumetanide Injection, USP

2.5 mg/10 mL (0.25 mg/mL)

10 mL Multiple Dose Vial

NDC 70748-323-02

Bumetanide Injection, USP

2.5 mg/10 mL (0.25 mg/mL)

10 x 10 mL Multiple Dose Vials

NDC 70748-323-11

What is Aldactone?

Aldactone is a potassium-sparing diuretic (water pill) that prevents your body from absorbing too much salt and keeps your potassium levels from getting too low.

Aldactone is used to treat heart failure, high blood pressure (hypertension), or hypokalemia (low potassium levels in the blood).

Aldactone also treats fluid retention (edema) in people with congestive heart failure, cirrhosis of the liver, or a kidney disorder called nephrotic syndrome.

Aldactone is also used to diagnose or treat a condition in which you have too much aldosterone in your body. Aldosterone is a hormone produced by your adrenal glands to help regulate the salt and water balance in your body.

Warnings

You should use Aldactone with caution if you have kidney problems, high levels of potassium in your blood, Addison’s disease, if you are unable to urinate, or if you are also taking eplerenone.

Aldactone has caused tumors in animals but it is not known whether this could occur in people. Do not use this medicine for any condition that has not been checked by your doctor.

Before taking this medicine

You should not use Aldactone if you are allergic to spironolactone, or if you have:

• Addison’s disease (an adrenal gland disorder);
• high levels of potassium in your blood (hyperkalemia);
• if you are unable to urinate; or
• if you are also taking eplerenone.

To make sure Aldactone is safe for you, tell your doctor if you have:

• an electrolyte imbalance (such as low levels of calcium, magnesium, or sodium in your blood);
• kidney disease;
• liver disease; or
• heart disease.

Tell your doctor if you are pregnant or plan to become pregnant. Having congestive heart failure, cirrhosis, or uncontrolled high blood pressure during pregnancy may lead to medical problems in the mother or the baby. Your doctor should decide whether you take Aldactone if you are pregnant.

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.

How should I take Aldactone?

Take Aldactone exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Do not share this medicine with another person, even if they have the same symptoms you have.

You may take Aldactone with or without food, but take it the same way each time.

You will need frequent medical tests.

This medicine can affect the results of certain medical tests. Tell any doctor who treats you that you are using Aldactone.

If you need surgery, tell your surgeon you currently use this medicine. You may need to stop for a short time.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from heat, light, and moisture.

Dosing information

Usual Adult Dose of Aldactone for Edema:

25 to 200 mg orally per day in single or divided doses

Duration of therapy: When given as the sole diuretic, continue the initial dose for at least 5 days, after which the initial dose may be adjusted to an optimal maintenance dose.

Comments:

-A second diuretic that acts more proximally at the renal tubule may be added if adequate diuresis has not been achieved after 5 days. The dose of this drug should remain unchanged if a second diuretic is added.

Uses:

-Treatment of edematous conditions in patients with congestive heart failure who are only partially responsive to or intolerant of other therapeutic measures or who are taking digitalis when other therapies are considered inappropriate.

-Treatment of edematous conditions in patients with liver cirrhosis accompanied by edema and/or ascites.

-Treatment of edematous conditions in patients with nephrotic syndrome when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics do not provide an adequate response.

Usual Adult Dose of Aldactone for Hypertension:

Initial dose: 50 to 100 mg orally per day in single or divided doses

Duration of therapy: Treatment should be continued for at least 2 weeks to achieve a maximum response. Subsequently, the dose may be adjusted according to patient response.

Usual Adult Dose for Congestive Heart Failure:

Initial dose: 25 mg orally once a day assuming serum potassium is less than or equal to 5 mEq/L and serum creatinine is less than or equal to 2.5 mg/dL

Maintenance dose:

-Patients tolerant of initial dose: May increase to 50 mg orally once a day as clinically indicated

-Patients intolerant of initial dose: May decrease to 25 mg orally every other day

Use: To increase survival and reduce the need for hospitalization of severe heart failure patients (New York Heart Association [NYHA] class III to IV) when used in addition to standard therapy.

Usual Adult Dose for Primary Hyperaldosteronism:

Diagnostic dose:

-Long test: 400 mg orally per day for 3 to 4 weeks

-Short test: 400 mg orally per day for 4 days

Maintenance dose: 100 to 400 mg orally per day until surgery; may be used long-term at the lowest effective dose in patients deemed unsuitable for surgery.

Comments:

-For the long test, correction of hypokalemia and hypertension provides presumptive evidence of primary hyperaldosteronism.

-For the short test, increased serum potassium with this drug and a decrease upon discontinuation provide presumptive evidence of primary hyperaldosteronism.

Uses:

-Initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism while patients are on normal diets.

-Short-term preoperative treatment of patients with primary hyperaldosteronism.

-Long-term maintenance therapy for patients deemed unsuitable for surgery or those with idiopathic hyperaldosteronism.

Usual Adult Dose for Hypokalemia:

25 to 100 mg orally per day

Uses:

-Treatment of patients with hypokalemia when other measures are considered inappropriate or inadequate.

-Prophylaxis of hypokalemia in patients taking digitalis when other measures are considered inadequate or inappropriate.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line.

What to avoid

Drinking alcohol can increase certain side effects.

Do not use potassium supplements or salt substitutes, 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.

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Aldactone side effects

Get emergency medical help if you have signs of an allergic reaction to Aldactone: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• little or no urination;
• high potassium level – nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement; o
• signs of other electrolyte imbalances – increased thirst or urination, confusion, vomiting, muscle pain, slurred speech, severe weakness, numbness, loss of coordination, feeling unsteady.

Common Aldactone side effects may include:

• breast swelling or tenderness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect Aldactone?

Using Aldactone with other drugs that make you dizzy can worsen this effect. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all your other medicines, especially:

• colchicine;
• digoxin;
• lithium;
• loperamide;
• trimethoprim;
• heart or blood pressure medicine (especially another diuretic);
• medicine to prevent a blood clot; or