Losartan
Mechanism :
Losartan competitively inhibits the binding of angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands. Losartan is metabolized to its active metabolite, E-3174, which is 10 to 40 times more potent than losartan and acts as a non-competitive AT1 antagonist. Inhibition of angiotensin II binding to AT1 inhibits its AT1-mediated vasoconstrictive and aldosterone-secreting effects and results in decreased vascular resistance and blood pressure. Losartan is 1,000 times more selective for AT1 than AT2. Inhibition of aldosterone secretion may increase sodium and water excretion while decreasing potassium excretion. Losartan is effective for reducing blood pressure and may be used to treat essential hypertension, left ventricular hypertrophy and diabetic nephropathy.
Indication :
Contraindications :
Hypersensitivity to drug/class/component.
Caution if renal artery stenosis, renal impairment or hepatic impairment.
Caution if volume depletion, hyponatremia or severe CHF.
Dosing :
>6 years:
Start with 0.7 mg/kg PO OD up to 50 mg/day.
Max: 1.4 mg/kg/day, 100 mg/day.
Adverse Effect :
Serious Reactions: Angioedema, anaphylaxis, hypotension, hyperkalemia, renal impairment/failure, anemia, rhabdomyolysis, hepatitis.
Common Reactions: Diarrhea, fatigue/asthenia, hypoglycemia, anemia, musculoskeletal pain, chest pain, weakness, cough, hypotension, hyperkalemia, dyspepsia, dizziness.
Interaction :
Contraindicated:
Aliskiren
Avoid/Use Alternative:
Lithium
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Initial dose 25 mg and titrate according to response |
| <10 | Initial dose 25 mg and titrate according to response |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in GFR<10 mL/min |
| HD | Not dialysed. Dose as in GFR<10 mL/min |
| HDF/High flux | Not dialysed. Dose as in GFR<10 mL/min |
| CAV/VVHD | Not dialysed. Dose as in GFR=10– 20 mL/min |
Hepatic Dose :
Mild to moderate impairment: There are no pediatric specific dosing recommendations; however, it is advisable to initiate at a reduced dose.
Severe impairment: No data is available. It should not be given in patients with severe impairment.