Losartan Potassium

You should not use losartan if you are allergic to it.

If you have diabetes or kidney disease, you may not be able to take losartan if you are also taking a blood pressure medication that contains aliskiren (Amturnide, Tekturna, Tekamlo, or Valturna).

To make sure losartan is safe for you, tell your doctor if you have:

• kidney disease;
• liver disease;
• congestive heart failure;
• an electrolyte imbalance (such as low levels of potassium in your blood); or
• if you are dehydrated.

FDA pregnancy category D. Do not use if you are pregnant. Stop using and tell your doctor right away if you become pregnant. Losartan can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control.

It is not known whether losartan passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Your pharmacist can provide more information about losartan.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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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.

COZAAR 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 COZAAR 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 COZAAR and 3.7% of patients given placebo. In 4 clinical trials involving over 1000 patients on various doses (10-150 mg) of losartan potassium and over 300 patients given placebo, the adverse events that occurred in ≥2% of patients treated with COZAAR 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.

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

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.

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

In the Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study involving 1513 patients treated with COZAAR or placebo, the overall incidences of reported adverse events were similar for the two groups. Discontinuations of COZAAR because of side effects were similar to placebo (19% for COZAAR, 24% for placebo). The adverse events, regardless of drug relationship, reported with an incidence of ≥4% of patients treated with COZAAR 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.

Postmarketing Experience

The following additional adverse reactions have been reported in postmarketing experience with COZAAR. 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-Sch�nlein purpura, has been reported. Anaphylactic reactions have been reported.

Metabolic and Nutrition: Hyponatremia.

Musculoskeletal: Rhabdomyolysis.

Nervous system disorders: Dysgeusia.

Skin: Erythroderma.

Read the entire FDA prescribing information for Cozaar (Losartan Potassium)

Angiotensin II receptor (AT1) antagonist (i.e., angiotensin II receptor blocker, ARB).1 2

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents, including diuretics).1 2 500

Angiotensin II receptor antagonists are recommended as one of several preferred agents for the initial management of hypertension; other options include ACE inhibitors, calcium-channel blockers, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).500 501 502 503 504 515

Angiotensin II receptor antagonists or ACE inhibitors may be preferred in hypertensive patients with diabetes mellitus or chronic kidney disease; angiotensin II receptor antagonists also may be preferred, as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or post-MI.500 501 502 504 520 523 524 527 534 535 536 543

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to angiotensin II receptor antagonists.500 501 504 However, diminished response to an angiotensin II receptor antagonist is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.500 504

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

Prevention of Cardiovascular Morbidity and Mortality

Reduction of the risk of stroke in patients with hypertension and left ventricular hypertrophy.1 2 53

Evidence suggests that the benefit associated with such losartan-based antihypertensive therapy does not apply to black patients.1 20 53

Preliminary evidence suggests that aspirin therapy at baseline in patients receiving losartan may reduce the risk of combined cardiovascular death, stroke, and acute MI compared with aspirin therapy at baseline in patients receiving atenolol.54

Diabetic Nephropathy

Management of diabetic nephropathy manifested by elevated Scr and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes mellitus and hypertension.1 33

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.38 39 41 42 43 520 535 536

Heart Failure

Angiotensin II receptor antagonists have been used in the management of heart failure†.524 528 800

Because of their established benefits, ACE inhibitors have been the preferred drugs for inhibition of the renin-angiotensin-aldosterone (RAA) system in patients with heart failure and reduced left ventricular ejection fraction (LVEF); 524 however, some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.701 702 703 800

Angiotensin II receptor antagonists may be used as an alternative for those patients in whom an ACE inhibitor or ARNI is inappropriate.524 800

No additional therapeutic benefit when angiotensin II receptor antagonist used in combination with an ACE inhibitor.a

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced LVEF (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.800

Storage

Oral

2.5-mg/mL preparation of losartan potassium tablets in a mixture of syrup (Ora-Sweet) and suspending vehicle (Ora-Plus) (see Oral Administration under Dosage and Administration): Up to 30 days at 2–8°C.1

Tight container at 25°C (may be exposed to 15–30°C).1 2 Protect from light.1 2

• Risks of use during pregnancy.1 2 56 57

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 2

• Importance of advising patients not to use potassium supplements or salt substitutes containing potassium without consulting their clinician.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).1 2

• Importance of informing patients of other important precautionary information.1 2 (See Cautions.)