Losartan Potassium (Page 2 of 8)

5.2 Hypotension in Volume- or Salt-Depleted Patients

In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with losartan potassium tablets. Correct volume or salt depletion prior to administration of losartan potassium tablets [see Dosage and Administration (2.1)].

5.3 Renal Function Deterioration

Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on losartan potassium tablets. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan potassium tablets [see Drug Interactions (7.3) and Use in Specific Populations (8.7)].

5.4 Hyperkalemia

Monitor serum potassium periodically and treat appropriately. Dosage reduction or discontinuation of losartan potassium tablets may be required [see Adverse Reactions (6.1)].

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Hypertension

Losartan potassium has been evaluated for safety in more than 3300 adult patients treated for essential hypertension and 4058 patients/subjects overall. Over 1200 patients were treated for over 6 months and more than 800 for over one year.

Treatment with losartan potassium was well-tolerated with an overall incidence of adverse events similar to that of placebo. In controlled clinical trials, discontinuation of therapy for adverse events occurred in 2.3% of patients treated with losartan potassium and 3.7% of patients given placebo. In 4 clinical trials involving over 1000 patients on various doses (10 to 150 mg) of losartan potassium and over 300 patients given placebo, the adverse events that occurred in ≥2% of patients treated with losartan potassium and more commonly than placebo were: dizziness (3% vs. 2%), upper respiratory infection (8% vs. 7%), nasal congestion (2% vs. 1%), and back pain (2% vs. 1%).

The following less common adverse reactions have been reported:

Blood and lymphatic system disorders: Anemia.

Psychiatric disorders: Depression.

Nervous system disorders: Somnolence, headache, sleep disorders, paresthesia, migraine.

Ear and labyrinth disorders: Vertigo, tinnitus.

Cardiac disorders: Palpitations, syncope, atrial fibrillation, CVA.

Respiratory, thoracic and mediastinal disorders: Dyspnea.

Gastrointestinal disorders: Abdominal pain, constipation, nausea, vomiting.

Skin and subcutaneous tissue disorders: Urticaria, pruritus, rash, photosensitivity.

Musculoskeletal and connective tissue disorders: Myalgia, arthralgia.

Reproductive system and breast disorders: Impotence.

General disorders and administration site conditions: Edema.

Cough

Persistent dry cough (with an incidence of a few percent) has been associated with ACE-inhibitor use and in practice can be a cause of discontinuation of ACE-inhibitor therapy. Two prospective, parallel-group, double-blind, randomized, controlled trials were conducted to assess the effects of losartan on the incidence of cough in hypertensive patients who had experienced cough while receiving ACE-inhibitor therapy. Patients who had typical ACE-inhibitor cough when challenged with lisinopril, whose cough disappeared on placebo, were randomized to losartan 50 mg, lisinopril 20 mg, or either placebo (one study, n=97) or 25 mg hydrochlorothiazide (n=135). The double-blind treatment period lasted up to 8 weeks. The incidence of cough is shown in Table 1 below.

Table 1:
Study 1 * HCTZ Losartan Lisinopril
Cough Study 2 25% Placebo 17% Losartan 69% Lisinopril
Cough 35% 29% 62%

These studies demonstrate that the incidence of cough associated with losartan therapy, in a population that all had cough associated with ACE-inhibitor therapy, is similar to that associated with hydrochlorothiazide or placebo therapy.

Cases of cough, including positive re-challenges, have been reported with the use of losartan in postmarketing experience.

Hypertensive Patients with Left Ventricular Hypertrophy

In the Losartan Intervention for Endpoint (LIFE) study, adverse reactions with losartan potassium were similar to those reported previously for patients with hypertension.

Nephropathy in Type 2 Diabetic Patients

In the Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study involving 1513 patients treated with losartan potassium tablets or placebo, the overall incidences of reported adverse events were similar for the two groups. Discontinuations of losartan potassium tablets because of side effects were similar to placebo (19% for losartan potassium tablets, 24% for placebo). The adverse events, regardless of drug relationship, reported with an incidence of ≥4% of patients treated with losartan potassium tablets and occurring with ≥2% difference in the losartan group vs. placebo on a background of conventional antihypertensive therapy, were asthenia/fatigue, chest pain, hypotension, orthostatic hypotension, diarrhea, anemia, hyperkalemia, hypoglycemia, back pain, muscular weakness, and urinary tract infection.

6.2 Postmarketing Experience

The following additional adverse reactions have been reported in postmarketing experience with losartan potassium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure:

Digestive: Hepatitis.

General Disorders and Administration Site Conditions: Malaise.

Hematologic: Thrombocytopenia.

Hypersensitivity: 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. Vasculitis, including Henoch-SchÖnlein purpura, has been reported. Anaphylactic reactions have been reported.

Metabolic and Nutrition: Hyponatremia.

Musculoskeletal: Rhabdomyolysis.

Nervous system disorders: Dysgeusia.

Skin: Erythroderma.

7 DRUG INTERACTIONS

7.1 Agents Increasing Serum Potassium

Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

7.2 Lithium

Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use.

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