Lifezar

Losartan potassium (Lifezar) 50 mg Tablet: Aquamarine, capsule-shaped, film-coated tablet, bisected on one side and plain on the other side.
Losartan potassium (Lifezar) 100 mg Tablet: Aquamarine, oval-shaped, film-coated tablet, bisected on one side and plain on the other side.
Each tablet contains: Losartan potassium 50 mg or 100 mg.

Angiotensin II Receptor Blocker.
Pharmacology: Pharmacodynamics: 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 angiotensin II subtype 1 (AT₁) receptor found in many tissues such as vascular smooth muscles, adrenal gland, kidneys, and the heart. A second angiotensin II receptor has been identified as the AT₂ receptor subtype 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 that 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.
Losartan does not bind to or block other hormone receptors or ion channels important in cardiovascular regulation. Furthermore, losartan does not inhibit ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin). Angiotensin II receptor antagonism results in dose-related increases in plasma renin levels, angiotensin I and angiotensin II levels, and a decrease in plasma aldosterone concentration.
Pharmacokinetics: Losartan is well absorbed after oral administration. It undergoes presystemic metabolism, forming an active metabolite (E-3174) and other inactive metabolites. Systemic bioavailability of losartan tablets is about 33%. Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and in 3 to 4 hours, respectively. There is no clinically significant effect on the plasma concentration profile of losartan when the drug is administered with a meal.
Both losartan and its metabolite are highly bound (≥99%) to plasma proteins, primarily albumin. Losartan's volume of distribution is 34 L.
Plasma concentrations of the active metabolite are higher than those of losartan at all doses, C_max and AUC for E-3174 are about 2 and 5 to 8 times greater than the corresponding values for losartan itself.
After oral administration, plasma concentrations of losartan and its active metabolite decline polyexponentially with terminal half-lives of about 2 hours (1.5 to 2.5 hours) and 6 to 9 hours, respectively. As anticipated from their short half-lives, neither losartan nor its active metabolite accumulates significantly in plasma during once-daily dosing with 100 mg.
The plasma clearance of losartan and its active metabolite is approximately 600 mL/min and 50 mL/min, respectively. Losartan is extensively metabolized in the liver. Approximately 35% of an oral losartan dose is excreted in urine as unchanged compound and metabolites. Only 4% of the dose is eliminated unchanged via the kidneys. Renal clearance of losartan and its active metabolite is about 74 mL/min and 26 mL/min, respectively. Losartan and its metabolites are also eliminated by biliary excretion, with 58% of an oral dose recovered in the feces.

Hypertension: For the treatment of hypertension; may be used alone or in combination with other antihypertensives, including diuretics.
Hypertensive Patients with Left Ventricular Hypertrophy: Decreases the risk of cardiovascular morbidity and mortality as measured by the combined incidence of cardiovascular death, stroke, and myocardial infarction in hypertensive patients with left ventricular hypertrophy.
Heart Failure: Heart failure in patients who cannot tolerate an ACE inhibitor.
Nephropathy in Type 2 Diabetic Patients: For the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension.
Decreases the progression of nephropathy as measured by the occurrence of doubling serum creatinine, end stage renal disease (need for dialysis or renal transplantation), or death; Reduces proteinuria.

General Dosing Recommendations: Dosing must be individualized and adjusted according to blood pressure response.
May be administered with other antihypertensives.
May be taken with or without food. (See table.)

Click on icon to see table/diagram/image

There is limited data on overdosage with losartan in humans. Losartan overdose will most likely manifest as hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Institute symptomatic treatment and monitor vital signs if symptomatic hypotension occurs.
Losartan and its metabolite are not removed by hemodialysis.

Hypersensitivity to any component of the product.
Women who are pregnant, trying to get pregnant or suspect that they are pregnant.

Angiotensin II receptor blockers can cause injury and even death to the developing fetus when used in pregnancy during the second and third trimesters. Discontinue losartan as soon as possible upon detection of pregnancy.

Hypotension and Electrolyte/Fluid Imbalance: Symptomatic hypotension may be observed in patients who are intravascularly volume-depleted (e.g., those treated with high-dose diuretics). These conditions should be corrected before starting losartan therapy, or a lower starting dose should be used.
Monitor serum potassium levels in type 2 diabetic patients with nephropathy treated with an angiotensin II antagonist.
Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed.
Renal Disease: Due to inhibition of the renin-angiotensin-aldosterone system, changes in renal function including renal failure have been seen in susceptible patients (e.g., patients whose renal function is dependent on the renin-angiotensin-aldosterone system such as those with severe cardiac insufficiency, pre-existing renal dysfunction) treated with losartan; these changes in renal function may be reversible upon discontinuation of therapy in some patients.
Treatment with ACE inhibitors has been associated with oliguria and/or progressive azotemia, and (rarely) with acute renal failure and/or death in patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure). Similar outcomes have been observed with losartan.
In studies, ACE inhibitors may increase blood urea nitrogen (BUN) and serum creatinine in patients with unilateral or bilateral renal artery stenosis. Renal effects have been observed with losartan; these effects may be reversible upon discontinuation of therapy in some patients.
Liver disease: In patients with a history of liver impairment, a lower dose of losartan should be given since significantly increased plasma concentrations of the drug in cirrhotic patients have been observed in pharmacokinetic studies.
Potassium-sparing Diuretics/Supplements/Salt Substitute: Patients taking losartan should be advised not to use potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium without consulting a physician. (See Interactions.)
General: Treatment with drugs that affect the renin-angiotensin-aldosterone system has been associated with acute hypotension, azotemia, oliguria or, rarely, acute renal failure in patients whose vascular tone and renal function depend predominantly on the activity of this system (e.g., patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis). As with any antihypertensive agent, excessive hypotension in patients with ischemic cardiopathy or ischemic cerebrovascular disease could result in a myocardial infarction or stroke.
Use in Pregnancy & Lactation: See Use in Pregnancy & Lactation section for further information.
Use in Children: Losartan is not recommended in neonates and in children with glomerular filtration rate <30 mL/min/1.73 m², as no data are available. Losartan is also not recommended in children with hepatic impairment.
Use in the Elderly: There were no age-related differences in efficacy or safety profile of losartan.

Pregnancy: Pregnancy Category C (first trimester) and D (second and third trimesters).
Fetal/Neonatal Mortality and Morbidity: The use of drugs that act directly on the renin-angiotensin-aldosterone 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 observed, 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. Discontinue losartan as soon as possible when pregnancy is detected.
If oligohydramnios is observed, discontinue losartan unless it is considered life saving for the mother. Contraction stress testing (CST), a nonstress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. However, physicians and patients should be aware that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Infants with history 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 a means of reversing hypotension and/or substituting for disordered renal function.
Lactation: It is not known whether losartan is distributed in human milk. Discontinue breastfeeding or drug due to potential risk to breastfeeding infants, taking into consideration the importance of the drug to the mother.

Body as a Whole: Asthenia, chest pain, edema, facial edema, fatigue, fever, infection, influenza-like disease, orthostatic effects, syncope, trauma.
Cardiovascular: Angina pectoris, arrhythmias including atrial fibrillation, cerebrovascular event/accident, hypotension/orthostatic hypotension, myocardial infarction, second degree AV block, palpitation, sinus bradycardia, sternalgia, tachycardia, ventricular tachycardia, ventricular fibrillation.
Endocrine: Diabetic nephropathy, diabetic vascular disease.
Gastrointestinal: Abdominal pain, anorexia, constipation, dental pain, diarrhea, dry mouth, dyspepsia, flatulence, gastritis, nausea, vomiting.
Hematologics: Hemolysis, anemia, epistaxis, thrombocytopenia (rare).
Liver/Biliary: Liver function abnormalities, hepatitis (rare).
Metabolic and Nutritional and Laboratory Values: Gout, hyperkalemia, hypoglycemia, hyponatremia, weight gain; Elevations of the following: alanine aminotransferase (ALT), BUN, serum creatinine, liver enzymes and/or bilirubin; Reductions of the following: hemoglobin and hematocrit.
Musculoskeletal: Arthralgia, arthritis, fibromyalgia, joint swelling, myalgia, muscle cramps, muscle weakness, pain (back, arm, shoulder, hip, leg, knee, musculoskeletal), stiffness, rhabdomyolysis (rare).
Nervous System/Psychiatric: Dizziness, anxiety, anxiety disorder, ataxia, confusion, depression, dream abnormality, dysgeusia, headache, hypesthesia, insomnia, decreased libido, memory impairment, migraine, nervousness, panic disorder, paresthesia, peripheral neuropathy, sleep disorder, somnolence, tremor, vertigo.
Respiratory: Bronchitis, cough/dry cough, dyspnea, nasal congestion/respiratory congestion, pharyngeal discomfort, pharyngitis, rhinitis, sinusitis/sinus disorder, upper respiratory tract infections.
Skin: Anaphylactic reactions, angioedema (including swelling of the larynx and glossitis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue), alopecia, cellulitis, dermatitis, dry skin, ecchymosis, erythema, erythroderma, flushing, photosensitivity, pruritus, rash, sweating, superficial peeling of palms, urticaria, vasculitis including Henoch-Schonlein purpura (rare).
Special Senses: Blurred vision, burning/stinging in the eye, cataract, conjunctivitis, taste perversion, tinnitus, decreased visual acuity.
Urogenitals: Impotence, nocturia, urinary frequency, urinary tract infection.

Lithium: Concomitant use of losartan with lithium may decrease lithium excretion. Monitor carefully serum lithium levels during concomitant use.
Potassium-sparing Diuretics/Supplements/Salt Substitutes: As with other medicines that block angiotensin II or its effect, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium, may increase serum potassium.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) including Selective Cyclooxygenase-2 (COX-2) Inhibitors: The antihypertensive effect of angiotensin II receptor antagonists may be reduced when coadministered with NSAIDs such as selective COX-2 inhibitors and nonselective NSAIDs.
Concurrent administration of angiotensin II receptor antagonists with NSAIDs may result in an increased risk of worsening of renal function (including possible acute renal failure) and an increase in serum potassium, particularly in patients with poor pre-existing renal function. The combination should be administered with caution, especially in the elderly. Regularly monitor renal function after initiation of concomitant therapy and adequately hydrate patients.
Other Drugs: In studies, co-administration of losartan with other drugs such as hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole, and erythromycin showed no significant drug interactions. Rifampicin and fluconazole decreased the concentrations of losartan and its active metabolite.

Store at temperatures not exceeding 30°C.

Angiotensin II Antagonists

C09CA01 - losartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.

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