losartan potassium and hydrochlorothiazide

Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II)], is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT₁ receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland). There is also an AT₂ receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Both losartan and its principal active metabolite do not exhibit any partial agonist activity at the AT₁ receptor and have much greater affinity (about 1000-fold) for the AT₁ receptor than for the AT₂ receptor. In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT₁ receptor. The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the AT₁ receptor.

Neither losartan nor its active metabolite inhibits ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin); nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.

The mechanism of the antihypertensive effect of thiazides is unknown.

Losartan potassium and hydrochlorothiazide tablets are indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy of hypertension, except when the hypertension is severe enough that the value of achieving prompt blood pressure control exceeds the risk of initiating combination therapy in these patients (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects and DOSAGE AND ADMINISTRATION).

Losartan potassium and hydrochlorothiazide tablets are indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to Black patients. (See PRECAUTIONS, Race, CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Losartan Potassium, Reduction in the Risk of Stroke, Race, and DOSAGE AND ADMINISTRATION.)

Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature in patients who were taking angiotensin converting enzyme inhibitors. When pregnancy is detected, losartan potassium and hydrochlorothiazide tablets should be discontinued as soon as possible.

The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug.

These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester.

Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of losartan potassium and hydrochlorothiazide tablets as soon as possible.

Rarely (probably less often than once in every thousand pregnancies), no alternative to an angiotensin II receptor antagonist will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment.

If oligohydramnios is observed, losartan potassium and hydrochlorothiazide tablets should be discontinued unless they are considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Infants with histories of in utero exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function.

There was no evidence of teratogenicity in rats or rabbits treated with a maximum losartan potassium dose of 10 mg/kg/day in combination with 2.5 mg/kg/day of hydrochlorothiazide. At these dosages, respective exposures (AUCs) of losartan, its active metabolite, and hydrochlorothiazide in rabbits were approximately 5, 1.5, and 1.0 times those achieved in humans with 100 mg losartan in combination with 25 mg hydrochlorothiazide. AUC values for losartan, its active metabolite and hydrochlorothiazide, extrapolated from data obtained with losartan administered to rats at a dose of 50 mg/kg/day in combination with 12.5 mg/kg/day of hydrochlorothiazide, were approximately 6, 2, and 2 times greater than those achieved in humans with 100 mg of losartan in combination with 25 mg of hydrochlorothiazide. Fetal toxicity in rats, as evidenced by a slight increase in supernumerary ribs, was observed when females were treated prior to and throughout gestation with 10 mg/kg/day losartan in combination with 2.5 mg/kg/day hydrochlorothiazide. As also observed in studies with losartan alone, adverse fetal and neonatal effects, including decreased body weight, renal toxicity, and mortality, occurred when pregnant rats were treated during late gestation and/or lactation with 50 mg/kg/day losartan in combination with 12.5 mg/kg/day hydrochlorothiazide. Respective AUCs for losartan, its active metabolite, and hydrochlorothiazide at these dosages in rats were approximately 35, 10, and 10 times greater than those achieved in humans with the administration of 100 mg of losartan in combination with 25 mg hydrochlorothiazide. When hydrochlorothiazide was administered without losartan to pregnant mice and rats during their respective periods of major organogenesis, at doses up to 3000 and 1000 mg/kg/day, respectively, there was no evidence of harm to the fetus.

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

In patients who are intravascularly volume-depleted (e.g., those treated with diuretics), symptomatic hypotension may occur after initiation of therapy with losartan potassium and hydrochlorothiazide tablets. This condition should be corrected prior to administration of losartan potassium and hydrochlorothiazide tablets (see DOSAGE AND ADMINISTRATION).

Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.

Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Lithium generally should not be given with thiazides (see PRECAUTIONS, Drug Interactions, Hydrochlorothiazide, Lithium).

Hypersensitivity: Angioedema. See ADVERSE REACTIONS, Post-Marketing Experience.

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been reported in susceptible individuals treated with losartan; in some patients, these changes in renal function were reversible upon discontinuation of therapy.

In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar outcomes have been reported with losartan.

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN have been reported. Similar effects have been reported with losartan; in some patients, these effects were reversible upon discontinuation of therapy.

Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Pregnancy: Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to drugs that act on the renin-angiotensin system, and they should also be told that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.

Symptomatic Hypotension: A patient receiving losartan potassium and hydrochlorothiazide tablets should be cautioned that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to the prescribing physician. The patients should be told that if syncope occurs, losartan potassium and hydrochlorothiazide tablets should be discontinued until the physician has been consulted.

All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.

Potassium Supplements: A patient receiving losartan potassium and hydrochlorothiazide tablets should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician (see PRECAUTIONS, Drug Interactions, Losartan Potassium).

Pregnancy Categories C (first trimester) and D (second and third trimesters). See WARNINGS, Fetal/Neonatal Morbidity and Mortality.

It is not known whether losartan is excreted in human milk, but significant levels of losartan and its active metabolite were shown to be present in rat milk. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Safety and effectiveness of losartan potassium and hydrochlorothiazide tablets in pediatric patients have not been established.

In a controlled clinical study for the reduction in the combined risk of cardiovascular death, stroke, and myocardial infarction in hypertensive patients with left ventricular hypertrophy, 2857 patients (62%) were 65 years and over, while 808 patients (18%) were 75 years and over. In an effort to control blood pressure in this study, patients were coadministered losartan and hydrochlorothiazide 74% of the total time they were on study drug. No overall differences in effectiveness were observed between these patients and younger patients. Adverse events were somewhat more frequent in the elderly compared to non-elderly patients for both the losartan-hydrochlorothiazide and the control groups (see CLINICAL PHARMACOLOGY, Special Populations).

In the LIFE study, Black patients with hypertension and left ventricular hypertrophy had a lower risk of stroke on atenolol than on losartan (both cotreated with hydrochlorothiazide in the majority of patients). Given the difficulty in interpreting subset differences in large trials, it cannot be known whether the observed difference is the result of chance. However, the LIFE study does not provide evidence that the benefits of losartan on reducing the risk of cardiovascular events in hypertensive patients with left ventricular hypertrophy apply to Black patients. (See CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects; Losartan Potassium, Reduction in the Risk of Stroke.)

Other adverse experiences that have been reported with losartan, without regard to causality, are listed below:

Body as a Whole: chest pain, facial edema, fever, orthostatic effects, syncope; Cardiovascular: angina pectoris, arrhythmias including atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia and ventricular fibrillation, CVA, hypotension, myocardial infarction, second degree AV block; Digestive: anorexia, constipation, dental pain, dry mouth, dyspepsia, flatulence, gastritis, vomiting; General disorders and administration site conditions: malaise; Hematologic: anemia; Metabolic: gout; Musculoskeletal: arm pain, arthralgia, arthritis, fibromyalgia, hip pain, joint swelling, knee pain, leg pain, muscle cramps, muscle weakness, musculoskeletal pain, myalgia, shoulder pain, stiffness; Nervous System/Psychiatric: anxiety, anxiety disorder, ataxia, confusion, depression, dream abnormality, hypesthesia, insomnia, libido decreased, memory impairment, migraine, nervousness, panic disorder, paresthesia, peripheral neuropathy, sleep disorder, somnolence, tremor, vertigo; Respiratory: dyspnea, epistaxis, nasal congestion, pharyngeal discomfort, respiratory congestion, rhinitis, sinus disorder; Skin: alopecia, dermatitis, dry skin, ecchymosis, erythema, flushing, photosensitivity, pruritus, sweating, urticaria; Special Senses: blurred vision, burning/stinging in the eye, conjunctivitis, decrease in visual acuity, taste perversion, tinnitus; Urogenital: impotence, nocturia, urinary frequency, urinary tract infection.

Other adverse experiences that have been reported with hydrochlorothiazide, without regard to causality, are listed below:

Body as a Whole: weakness; Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation; Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia; Hypersensitivity: purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema; Metabolic: hyperglycemia, glycosuria, hyperuricemia; Musculoskeletal: muscle spasm; Nervous System/Psychiatric: restlessness; Renal: renal failure, renal dysfunction, interstitial nephritis; Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis; Special Senses: transient blurred vision, xanthopsia.

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 below.

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 post-marketing experience.

In a clinical study in patients with severe hypertension (SiDBP ≥110 mmHg), the overall pattern of adverse events reported through six weeks of follow-up was similar in patients treated with losartan potassium and hydrochlorothiazide tablets as initial therapy and in patients treated with losartan as initial therapy. There were no reported cases of syncope in either treatment group. There were 2 (0.6%) and 0 (0.0%) cases of hypotension reported in the group treated with losartan potassium and hydrochlorothiazide tablets and the group treated with losartan, respectively. There were 3 (0.8%) and 2 (1.2%) cases of increased serum creatinine (>0.5 mg/dL) in the group treated with losartan potassium and hydrochlorothiazide tablets and the group treated with losartan, respectively, during the same time period. (See CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Severe Hypertension.)

The following additional adverse reactions have been reported in post-marketing experience:

Digestive: Hepatitis has been reported rarely in patients treated with losartan.

Hemic: 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 with losartan. Anaphylactic reactions have been reported.

Metabolic and Nutrition: Hyperkalemia, hyponatremia have been reported with losartan.

Musculoskeletal: Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.

Respiratory: Dry cough (see above) has been reported with losartan.

Skin: Erythroderma has been reported with losartan.

In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of losartan potassium and hydrochlorothiazide tablets.

Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen (BUN) or serum creatinine were observed in 0.6 and 0.8 percent, respectively, of patients with essential hypertension treated with losartan potassium and hydrochlorothiazide tablets alone. No patient discontinued taking losartan potassium and hydrochlorothiazide tablets due to increased BUN. One patient discontinued taking losartan potassium and hydrochlorothiazide tablets due to a minor increase in serum creatinine.

Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.14 grams percent and 0.72 volume percent, respectively) occurred frequently in patients treated with losartan potassium and hydrochlorothiazide tablets, but were rarely of clinical importance. No patients were discontinued due to anemia.

Liver Function Tests: Occasional elevations of liver enzymes and/or serum bilirubin have occurred. In patients with essential hypertension treated with losartan potassium and hydrochlorothiazide tablets alone, no patients were discontinued due to these laboratory adverse experiences.

Serum Electrolytes: See PRECAUTIONS.

Significant lethality was observed in mice and rats after oral administration of 1000 mg/kg and 2000 mg/kg, respectively, about 44 and 170 times the maximum recommended human dose on a mg/m² basis.

Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted.

Neither losartan nor its active metabolite can be removed by hemodialysis.

The oral LD₅₀ of hydrochlorothiazide is greater than 10 g/kg in both mice and rats. The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.

Dosing must be individualized. The usual starting dose of losartan is 50 mg once daily, with 25 mg recommended for patients with intravascular volume depletion (e.g., patients treated with diuretics) (see WARNINGS, Hypotension — Volume-Depleted Patients) and patients with a history of hepatic impairment (see WARNINGS, Impaired Hepatic Function). Losartan can be administered once or twice daily at total daily doses of 25 to 100 mg. If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response.

Hydrochlorothiazide is effective in doses of 12.5 to 50 mg once daily and can be given at doses of 12.5 to 25 mg as losartan potassium and hydrochlorothiazide tablets.

To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

The side effects (see WARNINGS) of losartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of losartan and hydrochlorothiazide will be associated with both sets of dose-independent side effects.

Replacement Therapy: The combination may be substituted for the titrated components.

Dose Titration by Clinical Effect: A patient whose blood pressure is not adequately controlled with losartan monotherapy (see above) or hydrochlorothiazide alone may be switched to losartan potassium and hydrochlorothiazide tablets 50/12.5 mg (losartan 50 mg/hydrochlorothiazide 12.5 mg) once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets of losartan potassium and hydrochlorothiazide tablets 50/12.5 mg once daily or one tablet of losartan potassium and hydrochlorothiazide tablets 100/25 mg (losartan 100 mg/hydrochlorothiazide 25 mg) once daily. A patient whose blood pressure is not adequately controlled with losartan 100 mg monotherapy (see above) may be switched to losartan potassium and hydrochlorothiazide tablets 100/12.5 mg once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets of losartan potassium and hydrochlorothiazide tablets 50/12.5 mg once daily or one tablet of losartan potassium and hydrochlorothiazide tablets 100/25 mg (losartan 100 mg/hydrochlorothiazide 25 mg) once daily.

A patient whose blood pressure is inadequately controlled by 25 mg once daily of hydrochlorothiazide, or is controlled but who experiences hypokalemia with this regimen, may be switched to losartan potassium and hydrochlorothiazide tablets 50/12.5 mg (losartan 50 mg/hydrochlorothiazide 12.5 mg) once daily, reducing the dose of hydrochlorothiazide without reducing the overall expected antihypertensive response. The clinical response to losartan potassium and hydrochlorothiazide tablets 50/12.5 mg should be subsequently evaluated, and if blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets of losartan potassium and hydrochlorothiazide tablets 50/12.5 mg once daily or one tablet of losartan potassium and hydrochlorothiazide tablets 100/25 mg (losartan 100 mg/hydrochlorothiazide 25 mg) once daily.

The usual dose of losartan potassium and hydrochlorothiazide tablets is one tablet of losartan potassium and hydrochlorothiazide tablets 50/12.5 mg once daily. More than two tablets of losartan potassium and hydrochlorothiazide tablets 50/12.5 mg once daily or more than one tablet of losartan potassium and hydrochlorothiazide tablets 100/25 mg once daily is not recommended. The maximal antihypertensive effect is attained about 3 weeks after initiation of therapy.

Use in Patients with Renal Impairment: The usual regimens of therapy with losartan potassium and hydrochlorothiazide tablets may be followed as long as the patient's creatinine clearance is >30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so losartan potassium and hydrochlorothiazide tablets are not recommended.

Patients with Hepatic Impairment: Losartan potassium and hydrochlorothiazide tablets are not recommended for titration in patients with hepatic impairment (see WARNINGS, Impaired Hepatic Function) because the appropriate 25 mg starting dose of losartan cannot be given.

The starting dose of losartan potassium and hydrochlorothiazide tablets for initial treatment of severe hypertension is one tablet of losartan potassium and hydrochlorothiazide tablets 50/12.5 mg once daily (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects). For patients who do not respond adequately to losartan potassium and hydrochlorothiazide tablets 50/12.5 mg after 2 to 4 weeks of therapy, the dosage may be increased to one tablet of losartan potassium and hydrochlorothiazide tablets 100/25 mg once daily. The maximum dose is one tablet of losartan potassium and hydrochlorothiazide tablets 100/25 mg once daily. Losartan potassium and hydrochlorothiazide tablets are not recommended as initial therapy in patients with hepatic impairment (see WARNINGS, Impaired Hepatic Function) because the appropriate 25 mg starting dose of losartan cannot be given. They are also not recommended for use as initial therapy in patients with intravascular volume depletion (e.g., patients treated with diuretics, see WARNINGS, Hypotension—Volume-Depleted Patients).

Treatment should be initiated with losartan potassium tablets 50 mg once daily. Hydrochlorothiazide 12.5 mg should be added or losartan potassium and hydrochlorothiazide tablets 50/12.5 mg substituted if the blood pressure reduction is inadequate. If additional blood pressure reduction is needed, losartan potassium tablets 100 mg and hydrochlorothiazide 12.5 mg or losartan potassium and hydrochlorothiazide tablets 100/12.5 mg may be substituted, followed by losartan potassium tablets 100 mg and hydrochlorothiazide 25 mg or losartan potassium and hydrochlorothiazide tablets 100/25 mg. For further blood pressure reduction other antihypertensives should be added (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Losartan Potassium, Reduction in the Risk of Stroke).

Losartan potassium and hydrochlorothiazide tablets may be administered with other antihypertensive agents.

Losartan potassium and hydrochlorothiazide tablets may be administered with or without food.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Keep container tightly closed. Protect from light.

Manufactured by
MERCK SHARP & DOHME LTD.
Cramlington, Northumberland, UK NE23 3JU
for
Sandoz Inc.
Princeton, NJ 08540

Issued June 2010

9937101

Do not take losartan potassium and hydrochlorothiazide tablets if you are pregnant or plan to become pregnant. Losartan potassium and hydrochlorothiazide tablets can harm your unborn baby causing injury and even death. Stop taking losartan potassium and hydrochlorothiazide tablets if you become pregnant and call your doctor right away. If you plan to become pregnant, talk to your doctor about other treatment options before taking losartan potassium and hydrochlorothiazide tablets.

Losartan potassium and hydrochlorothiazide tablets contain 2 prescription medicines, an angiotensin receptor blocker (ARB) and a diuretic (water pill). They are used to:

• lower high blood pressure (hypertension). Losartan potassium and hydrochlorothiazide tablets are not usually the first medicine used to treat high blood pressure.
• lower the chance of stroke in patients with high blood pressure and a heart problem called left ventricular hypertrophy (LVH). Losartan potassium and hydrochlorothiazide tablets may not help Black patients with this problem.

Losartan potassium and hydrochlorothiazide tablets have not been studied in children less than 18 years old.

High Blood Pressure (hypertension) Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. The losartan ingredient in losartan potassium and hydrochlorothiazide tablets can help your blood vessels relax so your blood pressure is lower. The hydrochlorothiazide ingredient in losartan potassium and hydrochlorothiazide tablets works by making your kidneys pass more water and salt.

Left Ventricular Hypertrophy (LVH) is an enlargement of the walls of the left chamber of the heart (the heart’s main pumping chamber). LVH can happen from several things. High blood pressure is the most common cause of LVH.

Do not take losartan potassium and hydrochlorothiazide tablets if you:

• are allergic to any ingredients in losartan potassium and hydrochlorothiazide tablets. See a complete list of ingredients in losartan potassium and hydrochlorothiazide tablets at the end of this leaflet.
• are allergic to any sulfonamide-containing ("sulfa") medicines. Ask your doctor if you are not sure what sulfonamide-containing ("sulfa") medicines are.
• are not passing urine.

Tell your doctor about all your medical conditions including if you:

• are pregnant or planning to become pregnant. See "What is the most important information I should know about losartan potassium and hydrochlorothiazide tablets?"
• are breast-feeding or plan to breast-feed. Losartan potassium and hydrochlorothiazide tablets can pass into your milk and may harm your baby. You and your doctor should decide if you will take losartan potassium and hydrochlorothiazide tablets or breast-feed. You should not do both.
• have been vomiting (throwing up), having diarrhea, sweating a lot, or not drinking enough fluids. These could cause you to have low blood pressure.
• have liver problems
• have kidney problems
• have systemic lupus erythematosus (Lupus; SLE)
• have diabetes
• have asthma
• have gout
• have any allergies

Losartan potassium and hydrochlorothiazide tablets and certain other medicines may interact with each other. Especially tell your doctor if you are taking:

• potassium supplements
• salt substitutes containing potassium
• water pills (diuretics)
• lithium (a medicine used to treat a certain kind of depression)
• medicines used to treat pain and arthritis, called non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors.

Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.

• Take losartan potassium and hydrochlorothiazide tablets exactly as prescribed by your doctor. Your doctor may change your dose if needed.
• Losartan potassium and hydrochlorothiazide tablets can be taken with or without food.
• If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Just take the next dose at your regular time.
• If you take too many losartan potassium and hydrochlorothiazide tablets, call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away.
• Your doctor may do blood tests from time to time while you are taking losartan potassium and hydrochlorothiazide tablets.

Losartan potassium and hydrochlorothiazide tablets may cause the following side effects that may be serious:

• injury or death of unborn babies. See "What is the most important information I should know about losartan potassium and hydrochlorothiazide tablets?"
• allergic reaction. Symptoms of an allergic reaction are swelling of the face, lips, throat, or tongue. Get emergency medical help right away and stop taking losartan potassium and hydrochlorothiazide tablets.
• low blood pressure (hypotension). Low blood pressure may cause you to feel faint or dizzy. Lie down if you feel faint or dizzy. Call your doctor right away.
• a new or worsening condition called systemic lupus erythematosus (Lupus; SLE)
• if you have kidney problems, you may see a worsening in how well your kidneys work. Call your doctor if you get swelling in your feet, ankles, or hands, or unexplained weight gain.
• If you have liver problems, you may see a worsening in how well your liver works. Call your doctor if you get nausea, pain in the right upper stomach area (abdomen), yellow eyes or skin (which can be itchy).

The most common side effects of losartan potassium and hydrochlorothiazide tablets in people with high blood pressure are:

• "colds" (upper respiratory infection)
• dizziness
• stuffy nose
• back pain
• fast or irregular heartbeat (palpitations)
• rash

Tell your doctor if you get any side effect that bothers you or that won't go away. This is not a complete list of side effects. For a complete list, ask your doctor or pharmacist.

• Store losartan potassium and hydrochlorothiazide tablets at room temperature at 59°F to 86°F (15°C to 30°C).
• Keep losartan potassium and hydrochlorothiazide tablets in a tightly closed container, and keep losartan potassium and hydrochlorothiazide tablets out of the light.
• Keep losartan potassium and hydrochlorothiazide tablets and all medicines out of the reach of children.

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use losartan potassium and hydrochlorothiazide tablets for a condition for which it was not prescribed. Do not give losartan potassium and hydrochlorothiazide tablets to other people, even if they have the same symptoms that you have. They may harm them.

This leaflet summarizes the most important information about losartan potassium and hydrochlorothiazide tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information that is written for health professionals.

Active ingredients: losartan potassium, hydrochlorothiazide

Inactive ingredients:

microcrystalline cellulose, lactose hydrous, pregelatinized starch, magnesium stearate, hydroxypropyl cellulose, hypromellose, titanium dioxide. Losartan potassium and hydrochlorothiazide tablets 50/12.5 mg and losartan potassium and hydrochlorothiazide tablets 100/25 mg also contain D&C yellow No. 10 aluminum lake. Losartan potassium and hydrochlorothiazide tablets 50/12.5 mg, losartan potassium and hydrochlorothiazide tablets 100/12.5 mg, and losartan potassium and hydrochlorothiazide tablets 100/25 mg may also contain carnauba wax.

Manufactured by
MERCK SHARP & DOHME LTD.
Cramlington, Northumberland, UK NE23 3JU
for
Sandoz Inc.
Princeton, NJ 08540

Issued June 2010

9937101