Can lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) and hydrochlorothiazide (HCTZ) (thiazide diuretic) be taken together?

Lisinopril and Hydrochlorothiazide Combination Therapy for Hypertension

Yes, lisinopril and hydrochlorothiazide can be safely and effectively taken together, and this combination is actually recommended for patients with hypertension who need multiple medications to achieve blood pressure control. 1

Rationale for Combination Therapy

Lisinopril (an ACE inhibitor) and hydrochlorothiazide (a thiazide diuretic) work through complementary mechanisms:

• Lisinopril inhibits the renin-angiotensin-aldosterone system by blocking ACE, reducing angiotensin II formation and decreasing vasoconstriction
• Hydrochlorothiazide promotes sodium and water excretion, reducing blood volume
• When combined, these medications provide additive blood pressure-lowering effects 1, 2

The combination is particularly effective because thiazide diuretics may stimulate the renin-angiotensin-aldosterone system, and adding an ACE inhibitor like lisinopril blocks this compensatory response, resulting in enhanced blood pressure reduction 1.

Efficacy of Combination

• The combination of lisinopril and hydrochlorothiazide produces greater blood pressure reductions than either medication alone 3
• In clinical trials, mean blood pressure reductions (systolic/diastolic) after 12 weeks were:
  • Lisinopril alone: -16.6/-12.5 mmHg
  • Hydrochlorothiazide alone: -10.4/-6.8 mmHg
  • Lisinopril + Hydrochlorothiazide: -23.9/-18.2 mmHg 3

Dosing Considerations

When using this combination:

1. If starting with lisinopril alone and adding hydrochlorothiazide:

   • A low dose of hydrochlorothiazide (e.g., 12.5 mg) may be added if blood pressure is not controlled with lisinopril alone
   • After adding hydrochlorothiazide, it may be possible to reduce the lisinopril dose 2

2. If starting with both medications:

   • For patients already taking diuretics, the recommended starting dose of lisinopril is 5 mg once daily 2
   • For patients with stage 2 hypertension, starting with two drugs of different classes is recommended 1

Benefits of the Combination

1. Lisinopril attenuates potassium loss caused by hydrochlorothiazide, helping maintain electrolyte balance 2
2. The combination improves adherence by simplifying the treatment regimen 1
3. Fixed-dose combinations are available, further reducing pill burden 1

Precautions and Monitoring

1. Initial dosing: When starting lisinopril in patients already on diuretics, there is a risk of excessive blood pressure reduction. Consider:

   • Decreasing or discontinuing the diuretic before starting lisinopril
   • Increasing salt intake prior to initiating lisinopril
   • Starting with a lower dose of lisinopril (5 mg) 2

2. Electrolyte monitoring: Regular monitoring of serum potassium is recommended, as the combination can affect potassium levels:

   • Lisinopril alone may increase serum potassium by approximately 0.1 mEq/L
   • The combination of lisinopril and hydrochlorothiazide typically results in a mean decrease in serum potassium of 0.1 mEq/L 2

3. Renal function: Monitor renal function, particularly in patients with pre-existing renal impairment 2

Special Populations

• Black patients: Thiazide diuretics or calcium channel blockers are more effective as initial therapy than ACE inhibitors in black patients, but the combination of an ACE inhibitor with a thiazide diuretic produces similar BP lowering in blacks as in other racial or ethnic groups 1

• Elderly patients: These patients are at higher risk of hypotension and falls, and may require lower initial doses 4

• Pregnancy: ACE inhibitors like lisinopril are contraindicated during pregnancy due to risk of fetal harm 1

The lisinopril-hydrochlorothiazide combination is generally well-tolerated. Common adverse effects include dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), and orthostatic effects (3.2%) 5.

In conclusion, lisinopril and hydrochlorothiazide represent a rational and effective combination for hypertension management, providing complementary mechanisms of action and enhanced blood pressure control compared to monotherapy with either agent.