Diuril

DIURIL (chlorothiazide) is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.

DIURIL (chlorothiazide) has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.

DIURIL (chlorothiazide) is indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.

Routine use of diuretics during normal pregnancy 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 toxemia.

Edema during pregnancy may arise from pathologic causes or from the physiologic and mechanical consequences of pregnancy. Thiazides are indicated in pregnancy when edema is due to pathologic causes, just as they are in the absence of pregnancy (see PRECAUTIONS, Pregnancy). Dependent edema in pregnancy, resulting from restriction of venous return by the gravid uterus, is properly treated through elevation of the lower extremities and use of support stockings. Use of diuretics to lower intravascular volume in this instance is illogical and unnecessary. During normal pregnancy there is hypervolemia which is not harmful to the fetus or the mother in the absence of cardiovascular disease. However, it may be associated with edema, rarely generalized edema. If such edema causes discomfort, increased recumbency will often provide relief. Rarely this edema may cause extreme discomfort which is not relieved by rest. In these instances, a short course of diuretic therapy may provide relief and be appropriate.

The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity.

Body as a Whole: Weakness.

Cardiovascular: Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs).

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

Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia. Hypersensitivity: Anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura.

Metabolic: Electrolyte imbalance (see PRECAUTIONS), hyperglycemia, glycosuria, hyperuricemia.

Musculoskeletal: Muscle spasm.

Nervous System/Psychiatric: Vertigo, paresthesias, dizziness, headache, restlessness.

Renal: Renal failure, renal dysfunction, interstitial nephritis. (See WARNINGS.)

Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia.

Special Senses: Transient blurred vision, xanthopsia.

Urogenital: Impotence.

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

Diuril is a prescription medication used to treat high blood pressure and fluid retention caused by congestive heart failure, hepatic cirrhosis, kidney disease, estrogen, and corticosteroids.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Oak Pharmaceuticals, Inc. (Subsidiary of Akorn, Inc.)

• Salix Pharmaceuticals, Inc.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Diuril, there are no specific foods that you must exclude from your diet when receiving this medication.

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

Do not use this medication if you are allergic to chlorothiazide, or if you are unable to urinate.

If you have certain conditions, you may need a dose adjustment or special tests to safely take this medication. Before taking chlorothiazide, tell your doctor if you have:

• kidney disease;
• liver disease;
• asthma or allergies;
• gout;
• lupus;
• diabetes; or
• if you are allergic to sulfa drugs.

If you have any of these conditions, you may need a dose adjustment or special tests to safely take chlorothiazide.

FDA pregnancy category C. It is not known whether chlorothiazide is harmful to an unborn baby. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment.

Chlorothiazide can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Avoid drinking alcohol, which can increase some of the side effects of chlorothiazide.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Avoid becoming overheated or dehydrated during exercise and in hot weather. 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.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult 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;

• severe pain in your upper stomach spreading to your back;

• pale or yellowed skin, dark colored urine, fever, easy bruising or bleeding;

• high levels of calcium in your blood--nausea, vomiting, constipation, increased thirst or urination, muscle weakness, bone pain, confusion, lack of energy, or tired feeling;

• low levels of sodium in the body--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;

• other signs of an an electrolyte imbalance--dry mouth, thirst, nausea, vomiting, drowsiness, feeling weak or restless, muscle pain, fast heart rate, seizure (convulsions); or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• dizziness, spinning sensation;

• diarrhea, constipation, stomach cramps;

• blurred vision;

• muscle spasm; or

• impotence, sexual problems.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Contraindications

• Anuria.b 110 111

• Known hypersensitivity to hydrochlorothiazide, other thiazides, or any ingredient in the formulation.b

• Although manufacturers state allergy to other sulfonamide derivatives is a contraindication,110 111 evidence to support cross-sensitivity is limited, and history of sensitivity to sulfonamide anti-infectives (“sulfa sensitivity”) should not be considered an absolute contraindication.

Warnings/Precautions

Warnings

May potentiate effects of other hypotensive agents.110 111 Although additive or potentiated antihypertensive effect usually is used to therapeutic advantage,500 hypotension could occur.110 111 b (See Interactions.)

Possible exacerbation or activation of systemic lupus erythematosus.110 111

Generally, do not use with lithium salts.110 111 (See Interactions.)

Sensitivity Reactions

May occur with or without history of allergy or bronchial asthma.110 111

Sulfonamide cross-sensitivity unlikely. (See Contraindications under Cautions.)

General Precautions

Monitor for fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia).b 110 111

Observe for signs of electrolyte imbalance (e.g., dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, oliguria, muscle pains, cramps, muscular fatigue, hypotension, tachycardia, nausea, vomiting).110 111

Perform periodic serum electrolyte determinations (particularly of potassium, sodium, chloride, and bicarbonate); institute measures to maintain normal serum concentrations if necessary.b

Serum and urinary electrolyte measurements are especially important with diabetes mellitus, vomiting, diarrhea, parenteral fluid therapy, or expectations of excessive diuresis.b

Weekly (or more frequent) electrolyte measurement early in treatment; possible to extend interval between measurements to ≥3 months when electrolyte response has stabilized.b

May occur after brisk diuresis, when cirrhosis is present, or with prolonged therapy; inadequate oral electrolyte intake may contribute.110 111

May cause cardiac arrhythmias, exaggerate cardiac response to cardiac glycoside toxicity (increase ventricular irritability).110 111

Use potassium-sparing diuretics and/or potassium supplementation to avoid or treat hypokalemia.110 111

Generally mild, usually does not require specific treatment except in renal or hepatic impairment.110 111

Chloride replacement may be required for metabolic acidosis.109

Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate treatment usually is water restriction rather than salt administration except when hyponatremia is life-threatening.110 111

In actual salt depletion, appropriate replacement is treatment of choice.110 111

Hyperuricemia or, rarely, precipitation of gout may occur; generally avoid or use with caution in patients with history of gout or elevated uric acid concentrations.110 111 500 502

In diabetic patients, dosage adjustment of insulin or oral hypoglycemics may be required; hyperglycemia may occur and latent diabetes mellitus may become evident.110 111

Antihypertensive effect may be enhanced after sympathectomy.110 111

May increase magnesium urinary excretion, resulting in hypomagnesemia.110 111

May decrease calcium urinary excretion, cause slight intermittent serum calcium increase in absence of known calcium metabolism disorder; marked hypercalcemia may indicate hyperparathyroidism.110 111

Discontinue parathyroid tests.110 111

May increase cholesterol and triglyceride concentrations.110 111 109

Clinical importance of these changes is unknown.b Diet low in saturated fat and cholesterol usually compensates.b

Orthostatic hypotension occurs rarely.b

Specific Populations

Category C.110 111

Diuretics are considered second-line agents for control of chronic hypertension in pregnant women;142 500 if initiation of antihypertensive therapy is necessary in a pregnant woman, other antihypertensives (i.e., methyldopa, nifedipine, labetalol) are preferred.142 540

Edema associated with pregnancy generally responds well to thiazides except when caused by renal disease; however, routine use not recommended in pregnant women with mild edema who are otherwise healthy.b 110 111

Diuretics are not recommended for prevention or management of gestational hypertension or preeclampsia.141 539 540

Distributed into milk.h 110 111 141 Manufacturer states to discontinue nursing or the drug;110 111 however, considered to be compatible with breast-feeding.141

No controlled studies in children; use is supported by experience and published literature about hypertension treatment in children.110

Experience with IV chlorothiazide sodium in infants and children is limited, and IV use in this age group generally is not recommended.a 111

Elderly may be at increased risk of dilutional hyponatremia, especially underweight females with poor oral fluid and electrolyte intake or excessive low-sodium nutritional supplement intake.b (See Hyponatremia under Cautions.)

Use with caution in patients with hepatic impairment or progressive liver disease (particularly with associated potassium deficiency); electrolyte imbalance may precipitate hepatic coma.b 110 111

Discontinue immediately if signs of impending hepatic coma appear.b

Use with caution in severe renal impairment; thiazides decrease GFR and may precipitate azotemia.b 110 111 Effects may be cumulative in impaired renal function.b 110 111

Consider interruption or discontinuance if progressive renal impairment (rising nonprotein nitrogen, BUN, or Scr) occurs.110 111

Common Adverse Effects

Potassium depletion, hyperuricemia (usually asymptomatic; rarely leading to gout).b Hypochloremic alkalosis in patients at risk (e.g., hypokalemic patients).b Hyperglycemia and glycosuria in diabetics.b

• Exact mechanism of diuretic action is unclear; may act by altering metabolism of the tubular cells.b

• Enhances excretion of sodium, chloride, and water by interfering with the transport of sodium ions across the renal tubular epithelium.b

• Primary site of diuretic action appears to be the cortical diluting segment of the nephron.b

• GFR decreases, but unclear whether secondary to a direct effect on renal vasculature or to the decrease in intravascular fluid volume or an increase in tubular pressure caused by the inhibition of sodium and water reabsorption.b The fall in GFR is not important in the mechanism of action.b

• Enhances urinary excretion of potassium secondary to increased amount of sodium at distal tubular site of sodium-potassium exchange.b

• Increases urinary bicarbonate excretion (although to a lesser extent than chloride excretion) but change in urinary pH is usually minimal; diuretic efficacy is not affected by the acid-base balance of the patient.b

• Hypocalciuric effect is thought to result from a decrease in extracellular fluid (ECF) volume, although calcium reabsorption in the nephron may be increased; also, slight or intermittent elevations in serum calcium concentration.b

• Rate of uric acid excretion is decreased, probably because of competitive inhibition of uric acid secretion or a decrease in ECF volume and a secondary increase in uric acid reabsorption.b

• Hypotensive activity in hypertensive patients; also augments the action of other hypotensive agents.b Precise mechanism of hypotensive action has not been determined, but postulated that part of this effect is caused by direct arteriolar dilation.b

In the U.S.

• Diuril

Available Dosage Forms:

• Tablet
• Suspension

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Diuretic

Chemical Class: Thiazide

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Abdominal or stomach pain
• back, leg, or stomach pains
• black, tarry stools
• bleeding gums
• blistering, peeling, or loosening of skin
• bloating
• blood in urine or stools
• bloody urine
• blue lips and fingernails
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• chills
• clay-colored stools
• cloudy urine
• cold sweats
• confusion
• constipation
• cough or hoarseness
• coughing that sometimes produces a pink frothy sputum
• coughing up blood
• cracks in the skin
• darkened urine
• decrease in urine output or decrease in urine-concentrating ability
• decreased frequency or amount of urine
• diarrhea
• difficult, fast, or noisy breathing, sometimes with wheezing
• difficulty swallowing
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• dry mouth
• fast or irregular heartbeat
• fever
• flushed, dry skin
• fruit-like breath odor
• general body swelling
• general feeling of discomfort or illness
• general feeling of tiredness or weakness
• greatly decreased frequency of urination or amount of urine
• headache
• hives
• increased blood pressure
• increased hunger
• increased sweating
• increased thirst
• increased urination
• indigestion
• itching
• joint pain, stiffness, or swelling
• loss of appetite
• loss of heat from the body
• lower back or side pain
• muscle cramps or pain
• nausea or vomiting
• nosebleeds
• numbness, tingling, pain, or weakness in hands or feet
• pain in joints or muscles
• painful or difficult urination
• pains in stomach, side, or abdomen, possibly radiating to the back
• pale skin
• pinpoint red spots on skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rash
• red, irritated eyes
• red skin lesions, often with a purple center
• red, swollen skin
• redness, soreness, or itching skin
• scaly skin
• seizures
• shortness of breath
• sore throat
• sores, ulcers, or white spots on lips or in mouth
• sores, welting, or blisters
• sugar in the urine
• swelling of face, fingers, legs, ankles, feet, or lower legs
• swollen or painful glands
• tenderness of salivary glands
• thickening of bronchial secretions
• tightness in chest
• trembling
• troubled breathing
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight loss
• vomiting of blood
• weakness and heaviness of legs
• weight gain
• wheezing
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Cramping
• decreased interest in sexual intercourse
• difficulty having a bowel movement (stool)
• feeling of constant movement of self or surroundings
• hair loss, thinning of hair
• inability to have or keep an erection
• increased sensitivity of skin to sunlight
• loss in sexual ability, desire, drive, or performance
• muscle spasm
• pinpoint red or purple spots on skin
• redness or other discoloration of skin
• restlessness
• sensation of spinning
• severe sunburn
• weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.