Applies to hydrochlorothiazide / valsartan: oral tablet.

Serious side effects

Along with its needed effects, hydrochlorothiazide / valsartan 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 while taking hydrochlorothiazide / valsartan:

Less common

• Cold or flu-like symptoms
• difficulty with swallowing
• sore throat
• tender or swollen lymph nodes in the neck
• unusual tiredness or weakness

Rare

• Bloating or stomach pain
• blurred vision
• chills
• eye pain
• fainting
• fever
• flushing
• itching, pain, redness, or swelling of the eye or eyelid
• joint stiffness or swelling, especially if sudden
• nausea
• skin rash or hives
• trouble breathing
• vomiting
• watering of the eyes
• yellow eyes or skin

Incidence not known

• Confusion
• dark urine
• decreased urine output
• dizziness
• drowsiness
• dry mouth
• fast or irregular heartbeat
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• lightheadedness
• muscle cramps, spasms, pain, or stiffness
• nervousness
• numbness or tingling in the hands, feet, or lips
• persistent non-healing sore
• pink growth
• reddish patch or irritated area
• seizures
• shiny bump
• thirst
• weakness or heaviness of the legs
• white, yellow or waxy scar-like area

Other side effects

Some side effects of hydrochlorothiazide / valsartan 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:

Less common

• Cough
• diarrhea (mild)
• headache

Rare

• Anxiety
• increased sensitivity to sunlight
• increased sweating
• redness of the face or neck
• reduced sexual performance or drive

Incidence not known

• Hair loss or thinning of the hair

For Healthcare Professionals

Applies to hydrochlorothiazide / valsartan: oral tablet.

Nervous system

Common (1% to 10%): Headache, fatigue, dizziness

Rare (less than 0.1%): Vertigo, tinnitus^[Ref]

Hypersensitivity

Rare (less than 0.1%): Nausea, diarrhea, rash, acute pulmonary edema, interstitial nephritis or cystitis, anaphylaxis^[Ref]

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.^[Ref]

Renal

Rare (less than 0.1%): Renal insufficiency, azotemia^[Ref]

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.^[Ref]

Cardiovascular

Rare (less than 0.1%): Palpitations, chest pain, angioedema

Frequency not reported: Cardiac arrhythmias (including ventricular ectopy and complete AV heart block)^[Ref]

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.^[Ref]

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.^[Ref]

Common (1% to 10%): Cough (valsartan component)

Uncommon (0.1% to 1%): Dyspnea, acute pulmonary edema^[Ref]

Dermatologic

Frequency not reported: Erythema annular centrifugum, acute eczematous dermatitis, morbilliform, leukocytoclastic vasculitis, phototoxic dermatitis, subacute cutaneous lupus erythematosus-like condition, pruritus, rash^[Ref]

Metabolic

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.^[Ref]

Rare (0.01% to 0.1%): Hypokalemia, hyperkalemia, metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, elevated serum uric acid levels, elevated serum cholesterol^[Ref]

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).^[Ref]

Uncommon (0.1% to 1%): Diarrhea, constipation, appetite changes, dry mouth, dyspepsia, nausea, vomiting, flatulence, pancreatitis, cholecystitis^[Ref]

Immunologic

Rare (0.01% to 0.1%): Allergic vasculitis, hemolytic anemia^[Ref]

Endocrine

Frequency not reported: Glucose intolerance, altered lipid profile^[Ref]

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.^[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, muscle cramps, myalgia

Valsartan:

Postmarketing reports: Rhabdomyolysis^[Ref]

Hematologic

Common (1% to 10%): Neutropenia

Uncommon (0.1% to 1%): Hematocrit decreased, hemoglobin decreased

Rare (0.01% to 0.1%): Immune complex hemolytic anemia

Postmarketing reports: Thrombocytopenia^[Ref]

Psychiatric

Rare (less than 0.1%): Anxiety, depression, decreased libido, insomnia, paresthesias, somnolence^[Ref]

Genitourinary

Rare (less than 0.1%): Impotence, dysuria^[Ref]

Hepatic

Uncommon (0.1% to 1%): Increases in hepatic enzymes (usually reversible)^[Ref]

Ocular

Rare (less than 0.1%): Abnormal vision, idiosyncratic reactions to hydrochlorothiazide resulting in acute transient myopia and acute angle-closure glaucoma^[Ref]