In clinical trials with losartan potassium-hydrochlorothiazide, no adverse experiences peculiar to this combination drug have been observed. Adverse experiences have been limited to those that were reported previously with losartan potassium and/or hydrochlorothiazide. The overall incidence of adverse experiences reported with the combination was comparable to placebo. The percentage of discontinuations of therapy was also comparable to placebo.
In general, treatment with losartan potassium-hydrochlorothiazide was well tolerated. For the most part, adverse experiences have been mild and transient in nature and have not required discontinuation of therapy.
In controlled clinical trials for essential hypertension, dizziness was the only adverse experience reported as drug-related that occurred with an incidence greater than placebo in one percent or more of patients treated with losartan potassium-hydrochlorothiazide.
In a controlled clinical trial in hypertensive patients with left ventricular hypertrophy, losartan, often in combination with hydrochlorothiazide, was generally well tolerated. The most common drug-related side effects were dizziness, asthenia/fatigue and vertigo.
The following additional adverse reactions have been reported in post-marketing experience with HYZAAR and/or in clinical trials or post-marketing use with the individual components: Neoplasms Benign, malignant and unspecified (incl cysts and polyps): Non-melanoma skin cancer (basal cell carcinoma, squamous cell carcinoma).
Blood and lymphatic system disorders: Thrombocytopenia, anemia, aplastic and hemolytic anemia, leukopenia, agranulocytosis.
Immune system disorders: Anaphylactic reactions, angioedema including swelling of the larynx and glottis causing airway obstruction and/or swelling of the face, lips, pharynx and/or tongue has been reported rarely in patients treated with losartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors.
Metabolism and nutrition disorders: Anorexia, hyperglycemia, hyperuricemia, electrolyte imbalance including hyponatremia and hypokalemia.
Psychiatric disorders: Insomnia, restlessness.
Nervous system disorders: Dysgeusia, headache, migraine, paraesthesias.
Eye disorders: Xanthopsia, transient blurred vision.
Cardiac disorders: Palpitation, tachycardia.
Vascular disorders: Dose-related orthostatic effects, necrotizing angiitis (vasculitis) (cutaneous vasculitis).
Respiratory, thoracic and mediastinal disorders: Cough, nasal congestion, pharyngitis, sinus disorder, upper respiratory infection, respiratory distress (including pneumonitis and pulmonary edema).
Gastrointestinal disorders: Dyspepsia, abdominal pain, gastric irritation, cramping, diarrhea, constipation, nausea, vomiting, pancreatitis, sialoadenitis.
Hepato-biliary disorders: Hepatitis, jaundice (intrahepatic cholestatic jaundice).
Skin and subcutaneous tissue disorders: Rash, pruritus, purpura (including Henoch-Schoenlein purpura), toxic epidermal necrolysis, urticaria, erythroderma, photosensitivity, cutaneous lupus erythematosus.
Musculoskeletal and connective tissue disorders: Back pain, muscle cramps, muscle spasm, myalgia, arthralgia.
Renal and urinary disorders: Glycosuria, renal dysfunction, interstitial nephritis, renal failure.
Reproductive system and breast disorders: Erectile dysfunction/impotence.
General Disorders and administration site conditions: Chest pain, edema/swelling, malaise, fever, weakness.
Investigations: Liver function abnormalities.
Description of Selected Side Effects: Non-melanoma skin cancer (basal cell carcinoma, squamous cell carcinoma): Based on available data from epidemiological studies, a cumulative dose-dependent association between hydrochlorothiazide and non-melanoma skin cancer (BCC and SCC) has been observed.
The largest study included a population comprised of 71,533 cases of BCC and 8,629 cases of SCC matched to 1,430,833 and 172,462 population controls, respectively. High cumulative hydrochlorothiazide use (≥ 50,000 mg) was associated with an adjusted odds ratio (OR) of 1.29 (95% CI: 1.23-1.35) for BCC and 3.98 (95% CI: 3.68-4.31) for SCC. A cumulative dose-response relationship was observed for both BCC and SCC. Another study evaluated the association between lip cancer (SCC) and exposure to hydrochlorothiazide: 633 cases of lip cancer were matched with 63,067 population controls. A cumulative dose-response relationship was demonstrated with an adjusted OR of 2.1 (95% CI: 1.7-2.6) for ever-use, increasing to an OR of 3.9 (95% CI: 3.0-4.9) for high use (≥ 25,000 mg) and an OR of 7.7 (95% CI: 5.7-10.5) for the highest cumulative dose (≥ 100,000 mg).
Laboratory Test Findings: In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of losartan-hydrochlorothiazide. Hyperkalemia (serum potassium >5.5 mEq/L) occurred in 0.7% of patients, but in these trials, discontinuation of losartan-hydrochlorothiazide due to hyperkalemia was not necessary. Elevations of alanine aminotransferase (ALT) occurred rarely and usually resolved upon discontinuation of therapy.