Lanzaar

Lanzaar 50: Each tablet contains losartan potassium 50 mg.
Lanzaar 100: Each tablet contains losartan potassium 100 mg.

Pharmacodynamics: Mechanism of Action: Antihypertensive action: Losartan is an angiotensin II receptor (type AT₁) antagonist that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively and competitively blocking the binding of angiotensin II to the AT₁ receptor found in many tissues, including vascular smooth muscle.
Pharmacokinetics: Onset of action: 6 hours.
Distribution: Vd: Losartan: 34 L; E-3174: 12 L; does not cross blood brain barrier.
Protein binding, plasma: High.
Metabolism: Hepatic (14%) via CYP2C9 and 3A4 to active metabolite, E-3174 (40 times more potent than losartan); extensive first-pass effect.
Bioavailability: 25% to 33%; AUC of E-3174 is four times greater than that of losartan.
Half-life elimination: Losartan: 1.5-2 hours; E-3174: 6-9 hours.
Time to peak, serum: Losartan: 1 hour; E-3174: 3-4 hours.
Excretion: Urine (4% as unchanged drug, 6% as active metabolite).
Clearance: Plasma: Losartan: 600 ml/minute; active metabolite: 50 ml/minute.

Treatment of hypertension (HTN); Treatment of diabetic nephropathy in patients with type 2 diabetes mellitus (NIDDM) and a history of hypertension; Stroke risk reduction in patients with HTN and left ventricular hypertrophy (LVH).

Recommended Doses: Hypertension: Children 6-16 years: 0.7 mg/kg once daily (maximum: 50 mg/day); adjust dose based on response; doses >1.4 mg/kg (maximum: 100 mg) have not been studied.
Adults: Usual starting dose: 50 mg once daily; can be administered once or twice daily with total daily doses ranging from 25-100 mg.
Patients receiving diuretics or with intravascular volume depletion: Usual initial dose: 25 mg.
Nephropathy in patients with type 2 diabetes and hypertension: Adults: Initial: 50 mg once daily; can be increased to 100 mg once daily based on blood pressure response.
Stroke reduction (HTN with LVH): Adults: 50 mg once daily (maximum daily dose: 100 mg); may be used in combination with a thiazide diuretic.
Dosing adjustment in renal impairment: Children: Use is not recommended if GFR<30 mL/minute/1.73 m².
Adults: No adjustment necessary.
Dosing adjustment in hepatic impairment: Children: No specific dosing recommendations, however it may be advisable to initiate therapy at a reduced dosage.
Adults: Reduce the initial dose to 25 mg/day; divide dosage intervals into two.
Mode of Administration: May be administered with or without food.

Symptoms including hypotension and tachycardia may occur with very significant overdoses.
Treatment: Treatment should be supportive. Not removed via hemodialysis.

Hypersensitivity to losartan or any component of the formulation.
Hypersensitivity to other angiotensin II receptor antagonists.
Pregnancy.
Concomitant use with aliskiren (renin inhibitor) in patients with diabetes mellitus.

Do not use this drug in pregnancy.
Consult physician if depression, nausea, or vomiting occur.
Discontinue this drug if angioedema of the face, tongue, glottis, or difficulty in breathing occurs, then consult physician immediately.
This drug may cause renal failure. Use cautiously in patients.
This drug may result in elevated potassium levels. Do not use this drug in patients who receive potassium or potassium-sparing diuretics.

Avoid use or use a much smaller dose in patients who are volume-depleted; correct depletion first.
Use with caution in patients with pre-existing renal insufficiency or significant aortic/mitral stenosis.
Use caution in patients with unilateral or bilateral renal artery stenosis to avoid a decrease in renal function.
AUCs of losartan (not the active metabolite) are about 50% greater in patients with Cl_cr <30 ml/minute and are doubled in hemodialysis patients.
When used to reduce the risk of stroke in patients with HTN and LVH, may not be effective in African-American population.
Use caution with hepatic dysfunction, dose adjustment may be needed.

Pregnancy: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
Lactation: Excretion in breast milk unknown/not recommended.

>10%: Cardiovascular: Chest pain (12% diabetic nephropathy).
Central nervous system: Fatigue (14% diabetic nephropathy).
Endocrine: Hypoglycemia (14% diabetic nephropathy).
Gastrointestinal: Diarrhea (2% hypertension to 15% diabetic nephropathy).
Genitourinary: Urinary tract infection (13% diabetic nephropathy).
Hematologic: Anemia (14% diabetic nephropathy).
Neuromuscular & skeletal: Weakness (14% diabetic nephropathy), back pain (2% hypertension to 12% diabetic nephropathy).
Respiratory: Cough (≤3% to 11%; similar to placebo; incidence higher in patients with previous cough related to ACE inhibitor therapy).
1% to 10%: Cardiovascular: Hypotension (7% diabetic nephropathy), orthostatic hypotension (4% hypertension to 4% diabetic nephropathy), first-dose hypotension (dose related: <1% with 50 mg, 2% with 100 mg).
Central nervous system: Dizziness (4%), hypoesthesia (5% diabetic nephropathy), fever (4% diabetic nephropathy), insomnia (1%).
Dermatology: Cellulitis (7% diabetic nephropathy).
Endocrine: Hyperkalemia (<1% hypertension to 7% diabetic nephropathy).
Gastrointestinal: Gastritis (5% diabetic nephropathy), weight gain (4% diabetic nephropathy), dyspepsia (1% to 4%), abdominal pain (2%), nausea (2%).
Neuromuscular & skeletal: Muscular weakness (7% diabetic nephropathy), knee pain (5% diabetic nephropathy), leg pain (1% to 5%), muscle cramps (1%), myalgia (1%).
Respiratory: Bronchitis (10% diabetic nephropathy), upper respiratory infection (8%), nasal congestion (2%), sinusitis (1% hypertension to 6% diabetic nephropathy).
Miscellaneous: Infection (5% diabetic nephropathy), flu-like syndrome (10% diabetic nephropathy).
<1% (Limited to important or life-threatening): Acute psychosis with paranoid delusions, ageusia, allergic reaction, alopecia, anaphylactic reactions, anemia, angina, angioedema, anorexia, anxiety, arrhythmia, arthralgia, arthritis, ataxia, AV block (second degree), bilirubin increased, blurred vision, bradycardia, bronchitis, BUN increased, confusion, conjunctivitis, constipation, CVA, depression, dermatitis, dysgeusia, dyspnea, ecchymosis, epistaxis, erythroderma, erythema, facial edema, fever, flatulence, flushing, gout, hematocrit decreased, hemoglobin decreased, Henoch-SchÖnlein purpura, hepatitis, hyponatremia, hypotension, impotence, joint swelling, maculopapular rash, malaise, memory impairment, MI, migraine, muscle weakness, myositis, neoplasm, nervousness, orthostatic effects, panic disorder, pancreatitis, paresthesia, peripheral neuropathy, pharyngitis, photosensitivity, pruritus, rash, rhabdomyolysis, rhinitis, serum creatinine increased, sleep disorder, somnolence, syncope, tachycardia, taste perversion, thrombocytopenia, tinnitus, transaminases increased, tremor, urinary frequency, urticaria, vasculitis, ventricular arrhythmia, vertigo, visual acuity decreased, vomiting, xerostomia.

Metabolism/Transport Effects: Substrate of CYP2C9 (major), CYP3A4 (major);
Inhibits CYP1A2 (weak), CYP2C19 (weak), CYP2C8 (moderate), CYP2C9 (moderate), CYP3A4 (weak).
Avoid Concomitant Use: Avoid concomitant use of losartan with any of the following: pimozide.
Increased Effect/Toxicity: Losartan may increase the levels/effects of: ACE Inhibitors; amifostine; antihypertensives; aripiprazole; carvedilol; cyclosporine (systemic); CYP2C8 substrates; CYP2C9 substrates; hypoglycemic agents; hypotensive agents; lithium; lomitapide; nonsteroidal anti-inflammatory agents; pimozide; potassium-sparing diuretics; rituximab; sodium phosphates.
The levels/effects of losartan may be increased by: alfuzosin; aliskiren; antifungal agents (azole derivatives, systemic); CYP2C9 inhibitors (moderate); CYP2C9 inhibitors (strong); diazoxide; eplerenone; fluconazole; herbs (hypoglycemic properties); herbs (hypotensive properties); MAO inhibitors; mifepristone; milk thistle; pentoxifylline; phosphodiesterase 5 inhibitors; potassium salts; prostacyclin analogues; salicylates; selective serotonin reuptake inhibitors; tolvaptan; trimethoprim.
Decreased Effect: The levels/effects of losartan may be decreased by: CYP2C9 inducers (strong); CYP3A4 inducers (strong); deferasirox; herbs (CYP3A4 inducers); herbs (hypertensive properties); loop diuretics; methylphenidate; nonsteroidal anti-inflammatory agents; peginterferon alfa-2b; rifamycin derivatives; tocilizumab; yohimbine.
Ethanol/Nutrition/Herb interactions: St John's wort may decrease level of losartan.
Some herbal medications may worsen hypertension (eg, licorice); others may increase the antihypertensive effect of losartan (eg, shepherd's purse).
Some herbal medications may increase the hypoglycemic effects of losartan (eg, alfalfa).
Management: Avoid St John's wort; Avoid bayberry; blue cohosh; ginseng (American); kola; licorice; and yohimbine; Avoid black cohosh; California poppy; coleus; golden seal; hawthorn; mistletoe; periwinkle; quinine and shepherd's purse; alfalfa; aloe; bilberry; bitter melon; burdock; celery; damiana; fenugreek; garcinia; garlic; ginger; gymnema; marshmallow; and stinging nettle.

Store below 30°C and protect from light.

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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