Valsartan/hydrochlorothiazide has been evaluated for safety in >4,300 patients. Adverse experiences have generally been mild and transient in nature. The following table of adverse experiences is based on 3 controlled trials involving a total of 7,616 patients. Of the 7,616 patients, 4,372 received valsartan in combination with hydrochlorothiazide. The overall incidence of adverse experiences with valsartan/hydrochlorothiazide was similar to placebo. All adverse experiences showing an incidence of ≥1% in the valsartan/hydrochlorothiazide group are included in the following table, irrespective of their causal association with the study drug. (See table.)
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Other adverse experiences with a frequency <1% included abdominal pain, anxiety, arthritis, asthenia, acute bronchitis, chest pain, postural dizziness, dyspepsia, dyspnea, dry mouth, erectile dysfunction, gastroenteritis, hyperhidrosis, hypesthesia, hypokalemia, hypotension, influenza, insomnia, muscle spasms and strain, nausea, nasal congestion, neck pain, edema, peripheral edema, otitis media, pain in extremity, palpitations, paresthesia, pharyngolaryngeal pain, pollakiuria, pyrexia, sinus congestion, sinusitis, somnolence, ligament sprain, syncope, tachycardia, tinnitus, urinary tract infection, vertigo, viral infection, blurred vision, vision disturbance. It is unknown whether these effects were casually related to the therapy.
Post-marketing data revealed very rare cases of angioneurotic edema, rash, pruritus and other hypersensitivity/allergic reactions including serum sickness and vasculitis. Very rare cases of renal impairment and myalgia have also been reported. There have also been reported several cases of hydrochlorothiazide-induced pulmonary edema with granulocytic infiltration and immunoglobulin G (IgG) deposition in alveolar membranes. Non-cardiogenic pulmonary edema may be an immunologically-mediated rare idiosyncratic reaction to hydrochlorothiazide.
Other additional adverse experiences reported in clinical trials with valsartan monotherapy, irrespective of their causal association with the study drug, were with a frequency <1%: Decreased libido, acute renal failure, occasional elevations in liver function values.
Hydrochlorothiazide has been extensively prescribed for many years, frequently in higher doses than those contained in valsartan/hydrochlorothiazide. The following adverse reactions have been reported in patients treated with thiazide diuretics alone including hydrochlorothiazide: Very Common:
Mainly at higher doses, hypokalemia, increased blood lipids.
Hyponatremia, hypomagnesemia, hyperuricemia, urticaria and other forms of rash, decreased appetite, mild nausea and vomiting, orthostatic hypotension, which may be aggravated by alcohol, anesthetics or sedatives, and impotence.
Hypercalcemia, hyperglycemia, glycosuria and worsening of diabetic metabolic state, photosensitivity reaction, abdominal discomfort, constipation, diarrhea, cholestasis or jaundice, arrhythmias, headache, dizziness, sleep disorders, depression, paresthesia, visual impairment, thrombocytopenia, sometimes with purpura.
Hypochloremic alkalosis, necrotizing vasculitis, toxic epidermal necrolysis, cutaneous lupus erythematosus-like reactions, reactivation of cutaneous lupus erythematosus, pancreatitis, leukopenia, agranulocytosis, bone marrow failure, hemolytic anemia, hypersensitivity reactions, respiratory distress including pneumonitis and pulmonary edema.
Adverse Drug Reactions from Post-Marketing Experiences:
The following adverse drug reactions have been identified based on post-marketing experiences. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequencies. Therefore, the frequency assigned is "not known".
Frequency Not Known:
Acute renal failure, renal disorder, aplastic anemia, erythema multiforme, pyrexia, muscle spasm, asthenia, acute angle-closure glaucoma.