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Lipika Samal M.D. and Paul A. Pham, Pharm.D.
04-23-2010
- Angiotensin receptor blockers (ARBs) are selective blockers of AT1 angiotensin receptors and work by blocking the binding of angiotensin II causing a decrease in systemic vascular resistance
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- Candesartan: Hypertension: 4-32 mg once daily initially and titrate to effect. Heart failure: Initial: 4 mg once daily. Titrate to effect by doubling dose every 3 weeks. Max dose 32 mg.
- Eprosartan: 600 mg once-daily initially (dose should individualized). Limited data on doses greater than 800 mg.
- Irbesartan: Hypertension: 150 mg once daily initially. Titrate to 300 mg once daily. Nephropathy: Target dose 300 mg once daily.
- Losartan: Hypertension: 50 mg once or twice daily, dose range 25-100 mg. Diabetic nephropathy: Initial: 50 mg once daily. Dose can be increased to 100 mg once daily based on blood pressure response. Stroke reduction: Initial: 50 mg once daily. Max dose 100 mg.
- Olmesartan: 20 mg once daily initially. Titrate to effect after two weeks, the dose may be increased to 40 mg once daily.
- Telmisartan: Hypertension: 40 mg once daily initially. Usual dose 20-80 mg daily Cardiovascular risk reduction: Initial: 80 mg daily
- Valsartan: Hypertension: 80-160 mg once daily initially. Max dose 320 mg daily. Cardiovascular risk reduction: 20 mg twice daily. Target dose 160 mg twice daily Heart failure: Initial: 40 mg twice daily. Typical doses between 80-160 mg twice daily. Max dose 320 mg daily.
- CrCl > 30 ml/min: no dosage adjustment is needed.
- For adults, no dosage adjustment needed, unless the patient is also volume-depleted.
- Initiate therapy with 25 mg PO once daily.
- FDA Category D. Avoid in pregnancy
- Black box warning: can cause injury or death to a developing fetus when used during the second and third trimesters.
- It is not known if losartan or its metabolite are excreted into breast milk; however, significant levels are present in rat milk. Breast-feeding is not recommended during losartan therapy because of the potential for adverse effects in the infant.
- Generally well tolerated.
- Hypotension
- Dyspepsia and diarrhea
- Dizziness
- Myalgia and muscle cramps
- Renal failure (CHF and volume depletion are risk factors)
- Malaise
- Rhabdomyolysis
- Cough (less likely compared to ACE inhibitors)
- Anaphylaxis and angioedema (less likely compared to ACE inhibitors)
- Impotence
- Allergic reactions
Losartan and irbesartan are CYP 1A2, 2C9, and 3A4 substrates. Valsartan and candesartan are only CYP2C9 substrates. Inhibitors and inducers of these CYP isoenzymes may increase and decrease the serum concentrations of these ARBs.
- Combination therapy with ACE inhibitors has been associated with an increased risk of diarrhea, hypotension, syncope, hyperkalemia, and renal dysfunction resulting in dialysis, and doubling of serum creatinine.
- Eplerenone, potassium-sparing diuretics and potassium supplements co-administration may result in hyperkalemia.
- Rifampin and phenobarbital may decrease all ARBs serum concentrations. Monitor for therapeutic efficacy and titrate to effect.
- CYP2C9 inhibitors (e.g. azole antifungals, fluoxetine, sertraline, amiodarone, cimetidine) may increase serum concentrations of valsartan and candesartan. Use lowest dose and monitor closely with co-administration.
- CYP1A2 inhibitors (e.g. ciprofloxacin and fluvoxamine) may increase serum concentrations of losartan and irbesartan. Use lowest dose and monitor closely with co-administration.
- CYP3A4 inhibitors (e.g. HIV protease inhibitors, azole antifungals, macrolide antibiotics) may increase serum concentrations of losartan and irbesartan. Use lowest dose and monitor closely with co-administration.
- Most ARBs are effective in the treatment of diabetic nephropathy (Lewis; Parving; Viberti; Brenner) and offer good alternatives for patients intolerant to ACE inhibitor (i.e. cough).
- Although more renal protection data is available with ACE inhibitors, a meta-analysis found that ARBs and ACE inhibitors have comparable efficacy (Sarafadis).
- Compared with ACE inhibitors, ARBs have less common occurrence of cough as a side effect, so are a reasonable alternative either as first choice or if patients develop cough using ACE inhibitors.
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