Diovan HCT Side Effects

Generic name: hydrochlorothiazide / valsartan

Note: This document contains side effect information about hydrochlorothiazide / valsartan. Some of the dosage forms listed on this page may not apply to the brand name Diovan HCT.

Some side effects of Diovan HCT may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to hydrochlorothiazide / valsartan: oral tablet

Get emergency medical help if you have any of these signs of an allergic reaction while taking hydrochlorothiazide / valsartan: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

In rare cases, hydrochlorothiazide and valsartan can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.

Stop using this medication and call your doctor at once if you have a serious side effect such as:

• eye pain, vision problems;

• feeling like you might pass out;

• urinating less than usual or not at all;

• weakness, increased thirst, loss of appetite, vomiting, pounding heartbeats or fluttering in your chest;

• swelling, weight gain, feeling short of breath;

• jaundice (yellowing of the skin or eyes); or

• dry mouth, increased thirst, drowsiness, restless feeling, confusion, increased urination, fast heart rate, fainting, or seizure (convulsions).

Less serious side effects of hydrochlorothiazide / valsartan may include:

• stomach pain, diarrhea;

• back pain;

• headache, tired feeling, dizziness;

• skin rash;

• stuffy nose, sore throat; or

• dry cough.

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

For Healthcare Professionals

Applies to hydrochlorothiazide / valsartan: oral tablet

General

Prior to approval by the FDA, valsartan-hydrochlorothiazide (HCTZ) was evaluated for safety in more than 1,300 patients, including over 360 treated for over 6 months, and 170 for over 1 year. Adverse experiences have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. The overall incidence of adverse experiences associated with the use of valsartan-HCTZ was comparable to placebo or to monotherapy with valsartan or hydrochlorothiazide. (Adverse experiences include adverse drug events.) The overall frequency of adverse experiences was neither dose-related nor related to gender, age, or race. In controlled clinical trials, discontinuation of therapy due to side effects was required in 3.6% of treated patients, compared with 4.3% of placebo patients. The most common reasons for withdrawal from therapy were headache, fatigue, and dizziness.

Nervous system

Nervous system side effects including fatigue and headache have been among the most common and have represented the most common reasons patients have discontinued therapy in controlled trials. Fatigue, headaches and dizziness have been reported in 5%, 2% and 9% of patients, respectively. Rarely, vertigo, tinnitus, abnormal vision, and extremely rare cases of stroke have been associated with the use of either of these drugs, alone or in combination. Stroke has rarely been associated with HCTZ-induced intravascular depletion and cerebrovascular insufficiency. Postmarketing clinical trials have revealed cases of syncope.

Hypersensitivity

Hypersensitivity reactions to either component of this combination drug have been rare, but potentially serious. Hypersensitivity reactions to valsartan and HCTZ have occurred in approximately 0.2% and 1.0% of patients, respectively. Hypersensitivity reactions have usually included nausea, diarrhea, and/or rash. Rare cases of acute pulmonary edema, interstitial nephritis or cystitis, and anaphylaxis have been associated with the use of HCTZ.

Rare cases of interstitial nephritis have been associated with the use of HCTZ. Although HCTZ has been used to treat nephrogenic diabetes insipidus, a case report in which the drug was believed to have caused this condition has been reported.

Renal

Renal side effects including new or worsened renal insufficiency have only rarely been associated with the use of valsartan-HCTZ. While valsartan monotherapy has not been associated with significant improvements or decrements in renal function, use of HCTZ can cause pre-renal azotemia and a rise in serum creatinine. It is unknown whether the use of angiotensin II receptor inhibitors might be associated with the development of renal insufficiency in the same way ACE inhibitors are. Risk factors for the development of renal insufficiency associated with the use of ACE inhibitors include heart failure, intravascular hypovolemia or dehydration, renal artery stenosis, and underlying renal insufficiency.

In multiple-dose studies in hypertensive patients with stable renal insufficiency and renovascular hypertension, the use of valsartan alone had no clinically significant effects of glomerular filtrate rate, filtration fraction, creatinine clearance, or renal plasma flow. The use of HCTZ has been associated with the development of pre-renal azotemia. Pretreatment volume repletion is recommended prior to initiating therapy.

Cardiovascular

Chest pain was reported in more than 2% of patients who were taking this combination drug in controlled trials, but this incidence was not significantly different compared with the incidence of chest pain among placebo patients.

Cardiovascular side effects associated with the use of valsartan include dizziness related to orthostatic hypotension and (rarely) palpitations, chest pain, and angioedema. Volume repletion is recommended prior to starting therapy to minimize the risk of symptomatic hypotension. Dose-related orthostatic effects have been seen in 1% of patients who were taking valsartan-HCTZ. Cardiac arrhythmias, including ventricular ectopy and complete AV heart block, have been associated with hypokalemia and hyponatremia secondary to HCTZ. (HCTZ-induced hypokalemia is less likely with the addition of valsartan, an inhibitor of aldosterone.) Orthostatic hypotension may occur and may rarely be associated with syncope, particularly in the elderly.

Respiratory

Angiotensin II receptor blockade, unlike ACE inhibition, has no impact on the processing of peptides such as bradykinin and substance P, two peptides able to induce cough.

Bronchospasm, dyspnea, and epistaxis have rarely been associated with the use of this drug.

Respiratory side effects associated with valsartan have included cough and dyspnea. In contrast to angiotensin converting enzyme (ACE) inhibitors, the incidence of cough associated with valsartan is similar to placebo. The incidence of cough among ACE inhibitors, valsartan, and placebo-treated patients averaged 7.9%, 2.6%, and 1.5%, respectively, in a large controlled trial. Dyspnea has been associated with the use of valsartan in less than 1% of patients, and acute pulmonary edema, presumably due to hypersensitivity, has rarely been associated with the use of HCTZ.

Dermatologic

Dermatologic side effects have been rare and were probably due to the HCTZ component. Dermatologic reactions to thiazide-type diuretics have included erythema annular centrifugum, acute eczematous dermatitis, and morbilliform and leukocytoclastic vasculitis. Thiazides may induce phototoxic dermatitis. In addition, a rare, distinct entity with clinical and laboratory features indistinguishable from those of subacute cutaneous lupus erythematosus has been associated with the use of HCTZ. Pruritus and rash have rarely been associated with the use of valsartan. Postmarketing experience revealed cases of alopecia.

Metabolic

Metabolic side effects including hypokalemia, which has been associated with the use of HCTZ, is much less likely with the addition of valsartan because A-II inhibitors decrease serum aldosterone levels. By the same token, the mild hyperkalemia, although usually clinically insignificant, that may accompany the use of valsartan, is much less likely due to HCTZ-induced kaliuresis. (In the absence of HCTZ, use of valsartan has been associated with greater than 20% increases in baseline serum potassium in 4.4% of patients, compared with 2.9% of patients treated with placebo.) HCTZ can induce metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, and elevated serum uric acid levels. It may also increase serum cholesterol.

Since HCTZ may increase total serum cholesterol by 11%, LDL lipoprotein cholesterol by 12%, and VLDL lipoprotein cholesterol levels by 50%, and may reduce insulin secretion, it should be used with caution in diabetic patients and in those with hypercholesterolemia. True glucose intolerance may develop in approximately 3% of patients. It is typically reversible within six months after discontinuation of therapy.

Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may occur, but are usually clinically insignificant except in malnourished patients.

Gastrointestinal

Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in an increased risk of cholesterol gallstone formation. Reports of bowel strictures associated with thiazide ingestion were reported in the 1960s (although patients in these reports were on a combination HCTZ-potassium product).

Gastrointestinal side effects have been rare, and have included diarrhea, constipation, appetite changes, dry mouth, dyspepsia, nausea, vomiting, or flatulence in 0.1% to 5.0% of patients. In addition, rare cases of pancreatitis and cholecystitis have been associated with the use of HCTZ.

Immunologic

Immunologic side effects associated with the use of HCTZ have been rare, and have included allergic vasculitis and hemolytic anemia. There have been numerous case reports of patients developing a rash histologically identical to subacute cutaneous lupus following HCTZ administration.

Endocrine

Endocrinologic problems associated with the use of thiazide-type diuretics include glucose intolerance and a potentially deleterious effect on the lipid profile. This may be important in some patients with or who are at risk for diabetes or coronary artery disease.

Use of valsartan alone has not been associated with significant changes in serum lipids or glucose concentrations. However, use of HCTZ may be associated with increases in total serum cholesterol by 11%, LDL lipoprotein cholesterol by 12%, and VLDL lipoprotein cholesterol levels by 50%. In addition, use of HCTZ may be associated with reduced insulin secretion. Therefore, caution is recommended when giving this combination drug to diabetic patients or those with hypercholesterolemia.

Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may occur, but are usually clinically insignificant except in malnourished patients.

A prospective study of 34 patients who received oral thiazide diuretics for 14 years without interruption revealed significantly increased average fasting blood glucose levels. Withdrawal of thiazide therapy for 7 months in 10 of the patients resulted in average reductions of 10% in fasting blood glucose and 25% in 2-hour glucose tolerance test values. A control group was not reported.

Musculoskeletal

Musculoskeletal complaints have been reported in 1% to 6% of patients who were taking valsartan, and have included back pain, muscle cramps, and myalgias. Myalgias and chills have also rarely been associated with HCTZ-induced diuresis.

Hematologic

Hematologic side effects have been extremely rare. Greater than 20% decreases in hematocrit or hemoglobin have been observed in only 0.8% and 0.4% of patients, respectively, who were taking valsartan. Neutropenia was observed in 1.9% of patients receiving valsartan and 0.8% of patients treated with placebo in controlled trials. Rare cases of immune-complex hemolytic anemia have been associated with the use of HCTZ. Thrombocytopenia and vasculitis have been reported postmarketing experience with valsartan.

Psychiatric

Psychiatric problems have been rarely associated with the use of this drug and have included have included anxiety, depression, decreased libido, insomnia, paresthesias, and somnolence.

Genitourinary

Genitourinary complaints have been rare and have included impotence and dysuria.

Hepatic

Hepatic side effects including reversible (greater than 150%) increases in hepatic enzymes have been rarely associated with the use of valsartan. Less than 0.1% of patients from large-scale controlled trials discontinued valsartan due to increased liver function tests. Hepatitis has been rarely reported with valsartan.

Ocular

Ocular side effects have included idiosyncratic reactions to hydrochlorothiazide resulting in acute transient myopia and acute angle-closure glaucoma.

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