Dosing and uses of Cozaar (losartan)
Adult dosage forms and strengths
tablet
- 25mg
- 50mg
- 100mg
Hypertension
50 mg/day PO (25 mg/day in patients with possible intravascular depletion or receiving diuretics)
Dosage range: 25-100 mg/day PO in 1 or 2 daily doses
Diabetic Nephropathy
Type 2 diabetes and hypertension: 50-100 mg PO qDay
Hypertension and Left Ventricular Hypertrophy
50 mg PO qDay initially; may increase to 100 mg PO qDay; may use in combination with a thiazide diuretic
Marfan Syndrome (Orphan)
Orphan designation for treatment of Marfan syndrome
Orphan sponsor
- National Marfan Foundation, 22 Manhasset Ave, Port Washington, NY 11050
Dosing Considerations
Generally, adjust dosage monthly; adjust more aggressively in high-risk patients
Pediatric dosage forms and strengths
tablet
- 25mg
- 50mg
- 100mg
Hypertension
<6 years: Safety and efficacy not established
≥6 years: 0.7 mg/kg/day (up to 50 mg/day) PO initially; not to exceed 1.4 mg/kg/day (or 100 mg/day)
Oral suspension may be used
Cozaar (losartan) adverse (side) effects
>10%
Fatigue (14%)
Hypoglycemia (14%)
Anemia (14%)
Urinary tract infection (UTI) (13%)
Chest pain (12%)
Weakness (14%)
Diarrhea (2-15%)
Cough; incidence higher in previous cough related to angiotensin-converting enzyme (ACE) inhibitor therapy (3-11%)
1-10%
Upper respiratory tract infection (8%)
Hypotension (7%)
Dizziness (4%)
Cellulitis (7%)
Gastritis (5%)
Nausea (2%)
Frequency not defined
Angioedema
Edema/swelling
Hypotension in hypovolemic or diuretic-using patients
Asthenia
Headache
Malaise
Nausea
Abdominal pain
Hyperkalemia
Back pain
Worsening renal failure
Warnings
Black box warnings
Discontinue as soon as possible when pregnancy is detected; drug affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury or death (see Pregnancy and lactation)
Contraindications
Hypersensitivity
Coadministration with aliskiren in patients with diabetes mellitus
Cautions
Angioedema, volume-depletion, severe congestive heart failure (CHF), hepatic or renal impairment
Correct volume or salt depletion prior to administration
Increases risks of hypotension; hyperkalemia
Monitor renal function and potassium in susceptible patients
Discontinue immediately if patient is pregnant; potential risk of congenital malformations
Use with caution in renal artery stenosis; avoid in bilateral renal artery stenosis
Renal impairment reported
Increased heart failure-related morbidity in patients receiving ACE inhibitors and beta blockers concomitantly; such combination therapy is not recommended
Dual blockade of the renin-angiotensin-aldosterone system (ie, an angiotensin-receptor blocker [ARB] plus an ACE inhibitor) in patients with established atherosclerotic disease, heart failure, or diabetes with end-organ damage is associated with a higher frequency of hypotension, syncope, hyperkalemia, and altered renal function (including acute renal failure) in comparison with use of a single renin-angiotensin-aldosterone system agent; limit dual blockade to individually defined cases with close monitoring of renal function; closely monitor blood pressure
Risk of anaphylactic reactions or angioedema
Pregnancy and lactation
Pregnancy category: d
Use of drugs that act on the renin-angiotensin system during the 2nd and 3rd trimesters of pregnancy reduces renal function and increases fetal and neonatal morbidity and death
Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations
Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death
When pregnancy is detected, discontinue as soon as possible
Lactation: Unknown if excreted in milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cozaar (losartan)
Mechanism of action
Blocks binding of angiotensin II to type 1 angiotensin II receptors; blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II
Absorption
Bioavailability: 25%
Onset: 6 hr
Duration: 24 hr
Peak plasma time: 1-1.5 hr
Distribution
Protein bound: Losartan, 98.7%; E-3174, 99.8%
Vd: Losartan, 34 L; E-3174, 12 L
Metabolism
Metabolized by hepatic P450 enzyme CYP2C9
Metabolites: 5-Carboxylic acid (E-3174) (active metabolite; 40 times as potent as losartan in angiotensin II-blocking activity)
Elimination
Half-life: Losartan, 1.5-2 hr; E-3174, 6-9 hr; increased in end-stage renal failure or CHF
Dialyzable: HD, no; PD, no
Renal clearance: Losartan, 43-75 mL/min; E-3174, 18-25 mL/min
Total plasma clearance: Losartan, 600 mL/min; E-3174, 50 mL/min
Excretion: Urine (4%)
