Thalitone® (chlorthalidone USP) is an antihypertensive/diuretic supplied as 15 mg tablets for oral use. It is a monosulfamyl diuretic that differs chemically from thiazide diuretics in that a double ring system is incorporated in its structure. It is a racemic mixture of 2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl) benzenesulfonamide, with the following structural formula:

Chlorthalidone is practically insoluble in water, in ether and in chloroform; soluble in methanol; slightly soluble in alcohol.

The inactive ingredients are colloidal silicon dioxide, lactose, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate.

Last updated on RxList: 7/16/2008

Thalitone® (chlorthalidone USP) is indicated in the management of hypertension either alone or in combination with other antihypertensive drugs. Chlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.

Chlorthalidone has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome,acute glomeru-lonephritis,and chronic renal failure.

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 developed toxemia.

Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical consequences of pregnancy. Chlorthalidone is indicated in pregnancy when edema is due to pathologic causes just as it is in the absence of pregnancy (however, see WARNINGS below). 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 illogical and unnecessary. There is hypervolemia during normal pregnancy that is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease) but that 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.

Therapy should be initiated with the lowest possible dose,then titrated according to individual patient response. A single dose given in the morning with food is recommended; divided doses are unnecessary.

Hypertension

Therapy in most patients should be initiated with a single daily dose of 15 mg. If the response is insufficient after a suitable trial, the dosage may be increased to 30 mg and then to a single daily dose of 45-50 mg. If additional control is required,the addition of a second antihypertensive drug is recommended. Increases in serum uric acid and decreases in serum potassium are dose-related over the 15-50 mg/day range and beyond.

Edema

INITIATION: Adults, initially 30 to 60 mg daily or 60 mg on alternate days. Some patients may require 90 to 120 mg at these intervals or up to 120 mg daily.Dosages above this level, however, do not usually produce a greater response.

MAINTENANCE: Maintenance doses may often be lower than initial doses and should be adjusted according to the individual patient. Effectiveness is well sustained during continued use.

White, kidney-shaped, compressed tablets coded M/024 containing 15 mg of chlorthalidone in bottles of 100 (NDC 61570-024-01).

Storage: Store below 30°C (86°F).

Prescribing Information as of January 2004. Distributed by: Monarch Pharmaceuticals, Inc.,Bristol, TN 37620 (A wholly owned subsidiary of King Pharmaceuticals, Inc.) Manufactured by: King Pharmaceuticals, Inc., Bristol,TN 37620. FDA Rev date: 6/1/2004

Last updated on RxList: 7/16/2008

The following adverse reactions have been observed, but there is not enough systematic collection of data to support an estimate of their frequency.

Gastrointestinal System Reactions: anorexia, gastric irritation, nausea, vomiting, cramping, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis.

Central Nervous System Reactions: dizziness, vertigo, paresthesias, headache, xanthopsia.

Hematologic Reactions: leukopenia,agranulocytosis,thrombocytopenia, aplastic anemia.

Dermatologic-Hypersensitivity Reactions: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis) (cutaneous vasculitis), Lyell's syndrome (toxic epidermal necrolysis).

Cardiovascular Reaction: Orthostatic hypotension may occur and may be aggravated by alcohol,barbiturates or narcotics.

Other Adverse Reactions: hyperglycemia, glycosuria, hyperuricemia, muscle spasm,weakness,restlessness,impotence.

Whenever adverse reactions are moderate or severe, chlorthalidone dosage should be reduced or therapy withdrawn.

Chlorthalidone may add to or potentiate the action of other antihypertensive drugs.

Insulin requirements in diabetic patients may be increased, decreased or unchanged. Higher dosage of oral hypoglycemic agents may be required.

Chlorthalidone and related drugs may increase the responsiveness to tubocurarine.

Chlorthalidone and related drugs may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

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

Drug/Laboratory Test Interactions

Chlorthalidone and related drugs may decrease serum PBI levels without signs of thyroid disturbance.

Last updated on RxList: 7/16/2008

Thalitone® (chlorthalidone USP) should be used with caution in severe renal disease. In patients with renal disease, chlorthalidone or related drugs may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

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

Sensitivity reactions may occur in patients with a history of allergy or bronchial asthma.

The possibility of exacerbation or activation of systemic lupus erythematosus has been reported with thiazide diuretics which are structurally related to chlorthalidone. However, systemic lupus erythematosus has not been reported following chlorthalidone administration.

General

Hypokalemia and other electrolyte abnormalities, including hyponatremia and hypochloremic alkalosis, are common in patients receiving chlorthalidone. These abnormalities are dose-related but may occur even at the lowest marketed doses of chlorthalidone. Serum electrolytes should be determined before initiating therapy and at periodic intervals during therapy.Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. All patients taking chlorthalidone should be observed for clinical signs of electrolyte imbalance, including dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, palpitations and gastrointestinal disturbances, such as nausea and vomiting. Digitalis therapy may exaggerate metabolic effects of hypokalemia especially with reference to myocardial activity.

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.

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

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

Uric Acid

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

Other

Increases in serum glucose may occur and latent diabetes melli-tus may become manifest during chlorthalidone therapy (see PRECAUTIONS: DRUG INTERACTIONS). Chlorthalidone and related drugs may decrease serum PBI levels without signs of thyroid disturbance.

Laboratory Tests

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

All patients receiving chlorthalidone should be observed for clinical signs of fluid or electrolyte imbalance: namely, hyponatremia, hypochloremic alkalosis and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No information is available.

Pregnancy/Teratogenic Effects

PREGNANCY CATEGORY B: Reproduction studies have been performed in the rat and the rabbit at doses up to 420 times the human dose and have revealed no evidence of harm to the fetus due to chlorthalidone. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Pregnancy/Non-Teratogenic Effects

Thiazides cross the placental barrier and appear in cord blood.The use of chlorthalidone and related drugs in pregnant women requires that the anticipated benefits of the drug be weighed against possible hazards to the fetus.These hazards include fetal or neonatal jaundice,thrombocytopenia,and possibly other adverse reactions that have occurred in the adult.

Nursing Mothers

Thiazides are excreted in human milk.Because of the potential for serious adverse reactions in nursing infants from chlorthalidone,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 in children have not been established.

Geriatric Use

Clinical studies of Thalitone® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond 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.

Last updated on RxList: 7/16/2008

Symptoms of acute overdosage include nausea, weakness, dizziness and disturbances of electrolyte balance.The oral LD50 of the drug in the mouse and the rat is more than 25,000 mg/kg body weight.The minimum lethal dose (MLD) in humans has not been established.There is no specific antidote but gastric lavage is recommended, followed by supportive treatment. Where necessary, this may include intravenous dextrose-saline with potassium,administered with caution.

Anuria. Known hypersensitivity to chlorthalidone or other sulfonamide-derived drugs.

Last updated on RxList: 7/16/2008

Chlorthalidone is a long-acting oral diuretic with antihypertensive activity. Its diuretic action commences a mean of 2.6 hours after dosing and continues for up to 72 hours.The drug produces diuresis with increased excretion of sodium and chloride.The diuretic effects of chlorthalidone and the benzothiadiazine (thiazide) diuretics appear to arise from similar mechanisms and the maximal effect of chlorthalidone and the thiazides appear to be similar. The site of the action appears to be the distal convoluted tubule of the nephron. The diuretic effects of chlorthalidone lead to decreased extracellular fluid volume, plasma volume, cardiac output, total exchangeable sodium, glomerular filtration rate, and renal plasma flow. Although the mechanism of action of chlorthalidone and related drugs is not wholly clear, sodium and water depletion appear to provide a basis for its antihypertensive effect. Like the thiazide diuretics, chlorthalidone produces dose-related reductions in serum potassium levels,elevations in serum uric acid and blood glucose, and it can lead to decreased sodium and chloride levels.

The mean plasma half-life of chlorthalidone is about 40 to 60 hours. It is eliminated primarily as unchanged drug in the urine.Non-renal routes of elimination have yet to be clarified. In the blood,approximately 75% of the drug is bound to plasma proteins.

Thalitone® (chlorthalidone USP) has been formulated with PVP (povidone polyvinylpyrrolidone), a bioavailability enhancer that provides 104% to 116% bioavailability relative to an oral solution of chlorthalidone. Thalitone® cannot be substituted for other formulations of chlorthalidone and likewise, other formulations of chlorthalidone cannot be substituted for Thalitone®.

Last updated on RxList: 7/16/2008

Patients should inform their doctor if they have: 1) had an allergic reaction to chlorthalidone or other diuretics or have asthma 2) kidney disease 3) liver disease 4) gout 5) systemic lupus erythematosus, or 6) been taking other drugs such as cortisone, digitalis,lithium carbonate,or drugs for diabetes.

Patients should be cautioned to contact their physician if they experience any of the following symptoms of potassium loss: excess thirst, tiredness, drowsiness, restlessness, muscle pains or cramps, nausea, vomiting or increased heart rate or pulse.

Patients should also be cautioned that taking alcohol can increase the chance of dizziness occurring.

Last updated on RxList: 7/16/2008

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.

CHLORTHALIDONE - ORAL

(klor-THAL-eh-doan)

COMMON BRAND NAME(S): Thalitone

USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Chlorthalidone is a "water pill" (diuretic) that causes your body to get rid of extra salt and water. This increases the amount of urine you make.

This medication also reduces extra fluid in the body (edema) caused by conditions such as congestive heart failure, liver disease, and kidney disease. Getting rid of extra water helps to reduce fluid in the lungs so that you can breathe easier. It also helps to decrease swelling of the arms, legs, and stomach/abdomen.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to treat a condition known as "water diabetes" (diabetes insipidus) and to help prevent calcium kidney stones.

HOW TO USE: Take this medication by mouth with or without food, usually once 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.

The dosage is based on your medical condition and response to therapy.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time each day or as prescribed. Do not increase your dose, skip doses, or stop taking this medication unless directed by your doctor. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick. For the treatment of high blood pressure, it may take up to several weeks before the full benefit of this drug takes effect.

Cholestyramine and colestipol can decrease the absorption of this medication by your body. If you are taking either of these drugs, separate them from chlorthalidone by at least 4 hours.

Inform your doctor if your condition does not improve or if it worsens (e.g., swelling increases, your routine blood pressure readings increase).

SIDE EFFECTS: Dizziness, lightheadedness, headache, blurred vision, loss of appetite, stomach upset, diarrhea, or constipation 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, notify your doctor or pharmacist promptly.

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

Tell your doctor immediately if any of these unlikely but serious side effects occur: numbness/tingling of the arms/legs, joint pain (e.g., big toe pain).

Tell your doctor immediately if any of these rare but very serious side effects occur: signs of infection (e.g., fever, persistent sore throat), easy bruising/bleeding, stomach/abdominal pain, persistent nausea/vomiting, unusual/persistent tiredness, yellowing eyes/skin, dark urine, unusual change in the amount of urine (not including the normal increase in urine when you first start this drug).

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, 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 chlorthalidone, tell your doctor or pharmacist if you are allergic to it; 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: severe kidney disease (inability to make urine).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, untreated salt/mineral imbalance (e.g., imbalance of sodium, potassium, calcium, magnesium), loss of too much body water (dehydration), high levels of fats in the blood (high cholesterol/triglycerides), gout, lupus, certain recent nerve surgery (sympathectomy).

If you have diabetes, chlorthalidone may affect your blood sugar levels. Check your blood sugar levels regularly as directed and share the results with 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 anti-diabetic medication or diet.

This drug may reduce the potassium levels in your blood. Ask your doctor about increasing the amount of potassium in your diet (e.g., bananas, orange juice) or about using a salt substitute containing potassium. A potassium supplement may be prescribed by your doctor.

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.

This drug may make you dizzy or cause blurred vision; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position. Significant loss of body water from too much sweating, vomiting, or diarrhea can also lower your blood pressure and worsen dizziness. Drink plenty of fluids to prevent these effects and dehydration. If you are on restricted fluid intake, consult your doctor for further instructions. Contact your doctor if you are unable to drink fluids or if you have persistent diarrhea/vomiting.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, the elderly may be more sensitive to the effects of this drug, especially dizziness.

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

This drug passes into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: See also the How to Use section.

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

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

If you are currently using any of these medications, tell your doctor or pharmacist before starting chlorthalidone.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: corticosteroids (e.g., prednisone), diazoxide, digoxin, lithium, nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, indomethacin), drugs that can increase dizziness (e.g., phenobarbital, narcotic pain relievers such as codeine).

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs for pain/fever reduction) because they may contain ingredients that could increase your blood pressure (e.g., pseudoephedrine, phenylephrine) or reduce the effect of this medication (e.g., ibuprofen, naproxen). Ask your pharmacist about the safe use of those products.

Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day) should be continued. Consult your doctor or pharmacist for more details.

This product can affect the results of certain lab tests. Make sure laboratory personnel and all 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. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: severe dizziness, severe weakness, fainting.

NOTES: Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise, and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Laboratory and/or medical tests (e.g., blood mineral levels such as potassium, kidney and liver function tests) should be performed from time to time 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 July 2008 Copyright(c) 2008 First DataBank, Inc.