Increasing Losartan to 100mg BID in CKD with Uncontrolled Hypertension
No, you should not increase losartan to 100mg twice daily—the maximum FDA-approved dose is 100mg once daily, not 200mg total daily. 1 Instead, optimize to losartan 100mg once daily and add a thiazide-type diuretic (chlorthalidone preferred) or increase the furosemide dose given the patient's CKD and already elevated loop diuretic requirement. 2
Critical Dosing Error to Avoid
- The FDA-approved maximum dose of losartan is 100mg once daily (total daily dose 100mg), not 100mg twice daily (200mg total). 1
- The ACC/AHA guidelines specify losartan target dose as 100mg once daily, though they note ACC/AHA recommends 150mg as target dose, the FDA maximum remains 100mg daily. 2
- Doses above 100mg daily have been studied in research settings but are not FDA-approved and should not be used in routine clinical practice. 1
Immediate Management for BP 188/104 mmHg
This patient requires prompt intensification given very high BP (≥180 systolic). 2
Step 1: Optimize Current Losartan Dose
- Increase losartan from 50mg BID (100mg total daily) to 100mg once daily. 1
- This maintains the same total daily dose but follows FDA-approved dosing schedule. 1
- Research shows 100mg daily is the optimal dose for both blood pressure reduction and renoprotection in diabetic nephropathy and CKD. 3, 4
Step 2: Add or Optimize Diuretic Therapy
Given CKD and current furosemide 40mg BID, consider:
- Increase furosemide to 80mg BID (loop diuretics are preferred over thiazides when GFR <30 mL/min). 2
- If GFR ≥30 mL/min, add chlorthalidone 12.5-25mg daily (preferred over hydrochlorothiazide for longer half-life and proven CVD reduction). 2
- Loop diuretics are specifically indicated in CKD with moderate-to-severe renal impairment. 2
Step 3: Consider Adding Spironolactone for Resistant Hypertension
If BP remains uncontrolled after optimizing losartan and diuretics:
- Add spironolactone 25mg daily as the recommended fourth agent for resistant hypertension (defined as uncontrolled BP on 3-drug regimen including RAS blocker, CCB would need to be added, and beta-blocker—carvedilol already on board). 5
- Monitor potassium and renal function within 1-2 weeks given CKD and concurrent losartan use. 5
- Avoid if GFR <45 mL/min or significant hyperkalemia risk. 2
Target Blood Pressure in CKD
- **Target BP <130/80 mmHg** (but >120/70 mmHg) in patients with CKD. 2
- In elderly patients (if applicable), target may be <140/80 mmHg. 2
Monitoring Requirements
Within 1 month:
- Recheck BP to assess response to medication intensification. 2
- Obtain basic metabolic panel to monitor potassium, creatinine, and eGFR. 2, 5
- Monitor for hyperkalemia (>6 mEq/L), which occurred in only 1% of CKD patients on losartan in clinical trials. 4
Ongoing:
- Monitor 24-hour creatinine clearance and proteinuria, as losartan provides renoprotection independent of BP lowering. 3, 6
- Losartan 100mg daily reduces albuminuria by 48% in diabetic nephropathy. 3
Why Not 100mg BID?
- No FDA approval exists for losartan doses exceeding 100mg daily. 1
- Research studies using 150mg daily showed no additional benefit over 100mg for albuminuria reduction (44% vs 48% reduction). 3
- The pharmacokinetics of losartan and its active metabolite E3174 (half-life 6-9 hours) support once-daily dosing. 7
- Twice-daily dosing at 100mg each (200mg total) would represent off-label use with no evidence of superior efficacy and potential for increased adverse effects. 1, 7
Additional Considerations
- Continue carvedilol 6.25mg BID—this is appropriate for heart failure if present, and beta-blockers are part of resistant hypertension regimens. 2, 5
- Continue aspirin 81mg daily for cardiovascular protection. 2
- Reinforce sodium restriction, which is particularly important in resistant hypertension and CKD. 5
- Losartan has been shown safe and well-tolerated in CKD patients, including those on hemodialysis, with stable creatinine clearance and GFR. 4, 8