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DIURIL®
(chlorothiazide) Oral Suspension
DIURIL (Chlorothiazide) is a diuretic and antihypertensive. It is 6-chloro-2 H-1,2,4-benzothiadiazine7-sulfonamide 1,1-dioxide. Its empirical formula is C7H6ClN3O4S2 and its structural formula is:
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It is a white, or practically white, crystalline powder with a molecular weight of 295.72, which is very slightly soluble in water, but readily soluble in dilute aqueous sodium hydroxide. It is soluble in urine to the extent of about 150 mg per 100 mL at pH 7.
DIURIL Oral Suspension contains 250 mg of chlorothiazide per 5 mL, alcohol 0.5 percent, with methylparaben 0.12 percent, propylparaben 0.02 percent, and benzoic acid 0.1 percent added as preservatives. The inactive ingredients are D&C Yellow 10, flavors, glycerin, purified water, sodium saccharin, sucrose and tragacanth.
Last updated on RxList: 6/24/2009
DIURIL is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.
DIURIL 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 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.
Therapy should be individualized according to patient response. Use the smallest dosage necessary to achieve the required response.
The usual adult dosage is 500 mg to 1000 mg (10 mL to 20 mL) once or twice a day. Many patients with edema respond to intermittent therapy, i.e., administration on alternate days or on three to five days each week. With an intermittent schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.
The usual adult starting dosage is 500 mg or 1000 mg (10 mL to 20 mL) a day as a single or divided dose. Dosage is increased or decreased according to blood pressure response. Rarely some patients may require up to 2000 mg (40 mL) a day in divided doses.
The usual pediatric dosage is 5 mg to 10 mg per pound (10 mg/kg to 20 mg/kg) per day in single or two divided doses, not to exceed 375 mg per day (2.5 mL to 7.5 mL or ˝ to 1˝ teaspoonfuls of the oral suspension daily) in infants up to 2 years of age or 1000 mg per day in children 2 to 12 years of age. In infants less than 6 months of age, doses up to 15 mg per pound (30 mg/kg) per day in two divided doses may be required. (See PRECAUTIONS, Pediatric Use.)
DIURIL Oral Suspension, 250 mg of chlorothiazide per 5 mL, is a yellow, creamy suspension, and is supplied as follows:
NDC 65649-311-12 bottles of 237 mL.
DIURIL Oral Suspension:Keep container tightly closed.Protect from freezing,–20°C (–4°F)and store at room temperature,15-30°C (59-86°F).
Manufactured by: Paddock Laboratories, Inc., Minneapolis, MN 55427. For: Salix Pharmaceuticals, Inc., Morrisville, NC 27560. May 2008.
Last updated on RxList: 6/24/2009
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.
When given concurrently the following drugs may interact with thiazide diuretics.
Alcohol, barbiturates, or narcotics - potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin) - dosage adjustment of the antidiabetic drug may be required.
Other antihypertensive drugs - additive effect or potentiation.
Cholestyramine and colestipol resins - Both cholestyramine and colestipol resins have the potential of binding thiazide diuretics and reducing diuretic absorption from the gastrointestinal tract.
Corticosteroids, ACTH -intensified electrolyte depletion, particularly hypokalemia.
Pressor amines (e.g., norepinephrine) - possible decreased response to pressor amines but not sufficient to preclude their use.
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) - possible increased responsiveness to the muscle relaxant.
Lithium - generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with DIURIL.
Non-steroidal Anti-inflammatory Drugs Including Selective Cyclooxygenase-2 (COX-2) Inhibitors - In some patients, the administration of a non-steroidal anti-inflammatory agent including a selective COX-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when DIURIL and non-steroidal anti-inflammatory agents or selective COX-2 inhibitors are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal antiinflammatory drugs, including selective COX-2 inhibitors, the co-administration of angiotensin II receptor antagonists or ACE inhibitors may result in a further deterioration of renal function, including possible acute renal failure. These effects are usually reversible.
These interactions should be considered in patients taking NSAIDs including selective COX-2 inhibitors concomitantly with diuretics and angiotensin II antagonists or ACE inhibitors. Therefore, the combination should be administered with caution, especially in the elderly.
Thiazides should be discontinued before carrying out tests for parathyroid function (see PRECAUTIONS, General).
Last updated on RxList: 6/24/2009
Use with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Thiazides may add to or potentiate the action of other antihypertensive drugs.
Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma. The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.
Lithium generally should not be given with diuretics (see PRECAUTIONS: DRUG INTERACTIONS ).
All patients receiving diuretic therapy should be observed for evidence 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. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.
Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present or after prolonged therapy.
Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmias and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Hypokalemia may be avoided or treated by use of potassium-sparing diuretics or potassium supplements such as foods with a high potassium content.
Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
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 actual salt depletion, appropriate replacement is the therapy of choice.
Hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazides.
In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy.
The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient.
If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at appropriate intervals.
Carcinogenicity studies have not been conducted with chlorothiazide.
Chlorothiazide was not mutagenic in vitro in the Ames microbial mutagen test (using a maximum concentration of 5 mg/plate and Salmonella typhimurium strains TA98 and TA100) and was not mutagenic and did not induce mitotic nondisjunction in diploid-strains of Aspergillus nidulans.
Chlorothiazide had no adverse effects on fertility in female rats at doses up to 60 mg/kg/day and no adverse effects on fertility in male rats at doses up to 40 mg/kg/day. These doses are 1.5 and 1 times** the recommended maximum human dose, respectively, when compared on a body weight basis.
Pregnancy Category C: Although reproduction studies performed with chlorothiazide doses of 50 mg/kg/day in rabbits, 60 mg/kg/day in rats and 500 mg/kg/day in mice revealed no external abnormalities of the fetus or impairment of growth and survival of the fetus due to chlorothiazide, such studies did not include complete examinations for visceral and skeletal abnormalities. It is not known whether chlorothiazide can cause fetal harm when administered to a pregnant woman; however, thiazides cross the placental barrier and appear in cord blood. DIURIL should be used during pregnancy only if clearly needed (see INDICATIONS AND USAGE).
Chlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult.
Because of the potential for serious adverse reactions in nursing infants from DIURIL, 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.
There are no well-controlled clinical trials in pediatric patients. Information on dosing in this age group is supported by evidence from empiric use in pediatric patients and published literature regarding the treatment of hypertension in such patients. (See DOSAGE AND ADMINISTRATION, Infants and Children.)
Clinical studies of DIURIL 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 (see WARNINGS).
** Calculations based on a human body weight of 50 kg
Last updated on RxList: 6/24/2009
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
In the event of overdosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. If required, give oxygen or artificial respiration for respiratory impairment.
The degree to which chlorothiazide sodium is removed by hemodialysis has not been established.
The oral LD50 of chlorothiazide is 8.5 g/kg, greater than 10 g/kg, and greater than 1 g/kg, in the mouse, rat and dog respectively.
Anuria.
Hypersensitivity to this product or to other sulfonamide-derived drugs.
Last updated on RxList: 6/24/2009
The mechanism of the antihypertensive effect of thiazides is unknown. DIURIL does not usually affect normal blood pressure.
DIURIL affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic efficacy.
DIURIL increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.
After oral use diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours.
DIURIL is not metabolized but is eliminated rapidly by the kidney. The plasma half-life of chlorothiazide is 45-120 minutes. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Last updated on RxList: 6/24/2009
No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.
Last updated on RxList: 6/24/2009
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.
CHLOROTHIAZIDE - ORAL
(klor-oh-THIGH-uh-zide)
COMMON BRAND NAME(S): Diuril
USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Chlorothiazide 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 or twice daily or as directed by your doctor. It is best to avoid taking this medication within 4 hours of your bedtime to avoid having to get up to urinate. Consult your doctor or pharmacist if you have questions about your dosing schedule.
If you are taking the suspension, shake the bottle well before each dose. Measure the dose carefully using a medication spoon/cup. Do not use a household spoon.
The dosage is based on your medical condition and response to therapy. In children, the dose is also based on age and weight. The manufacturer recommends that children younger than 2 years should not take more than 375 milligrams per day. Children 2-12 years old should not take more than 1,000 milligrams per day.
Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time(s) 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 chlorothiazide 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).
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 chlorothiazide, 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, chlorothiazide 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.
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 chlorothiazide.
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 in a tightly closed container at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Do not freeze the suspension. 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.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get tips on handling your hypertension.
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