Drug Interactions between fosinopril / hydrochlorothiazide and sildenafil

MONITOR: Although they are frequently combined in clinical practice, diuretics and angiotensin converting enzyme (ACE) inhibitors may have additive effects. Coadministration makes hypotension and hypovolemia more likely than does either drug alone. Some ACE inhibitors may attenuate the increase in the urinary excretion of sodium caused by some loop diuretics. Some patients on diuretics, especially those on dialysis or a dietary salt restriction, may experience acute hypotension with lightheadedness and dizziness after receiving the first dose of the ACE inhibitor. In addition, ACE inhibitors may cause renal insufficiency or acute renal failure in patients with sodium depletion or renal artery stenosis.

MANAGEMENT: Monitoring of blood pressure, diuresis, electrolytes, and renal function is recommended during coadministration. The possibility of first-dose hypotensive effects may be minimized by initiating therapy with small doses of the ACE inhibitor, or either discontinuing the diuretic temporarily or increasing the salt intake approximately one week prior to initiating an ACE inhibitor. Alternatively, the patient may remain under medical supervision for at least two hours after the first dose of the ACE inhibitor, or until blood pressure has stabilized.

MONITOR: Phosphodiesterase-5 (PDE5) inhibitors may potentiate the blood pressure-lowering effect of antihypertensive medications or medications with hypotensive properties, including vasodilators. These agents inhibit PDE5-mediated degradation of cyclic guanosine monophosphate (cGMP), which in vascular smooth muscles can lead to peripheral vasodilation and thus blood pressure (BP) reduction. For example, when sildenafil (100 mg) was coadministered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction in supine BP was 8/7 mmHg. Likewise, in a group of patients whose hypertension was controlled with nifedipine slow-release (30 mg or 60 mg) once daily, the addition of vardenafil (20 mg) produced a mean additional supine BP reduction of 6/5 mmHg compared to placebo. When coadministered with amlodipine (5 mg) daily or enalapril (20 mg) daily, a single dose of avanafil (200 mg) produced a mean maximum decrease in supine systolic BP of 1.2 mmHg (amlodipine) and supine BP of 1.8/3.5 mmHg (enalapril) compared to placebo.

MANAGEMENT: Caution is advised if PDE5 inhibitors are prescribed in combination with antihypertensive agents or agents with hypotensive properties. Patients receiving the combination should be advised to avoid rising abruptly from a sitting or recumbent position, especially following treatment initiation or a dosage increase, and to contact their doctor if they experience symptoms of hypotension such as dizziness, lightheadedness, fainting, or tachycardia.

MONITOR: Phosphodiesterase-5 (PDE5) inhibitors may potentiate the blood pressure-lowering effect of antihypertensive medications or medications with hypotensive properties, including vasodilators. These agents inhibit PDE5-mediated degradation of cyclic guanosine monophosphate (cGMP), which in vascular smooth muscles can lead to peripheral vasodilation and thus blood pressure (BP) reduction. For example, when sildenafil (100 mg) was coadministered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction in supine BP was 8/7 mmHg. Likewise, in a group of patients whose hypertension was controlled with nifedipine slow-release (30 mg or 60 mg) once daily, the addition of vardenafil (20 mg) produced a mean additional supine BP reduction of 6/5 mmHg compared to placebo. When coadministered with amlodipine (5 mg) daily or enalapril (20 mg) daily, a single dose of avanafil (200 mg) produced a mean maximum decrease in supine systolic BP of 1.2 mmHg (amlodipine) and supine BP of 1.8/3.5 mmHg (enalapril) compared to placebo.

MANAGEMENT: Caution is advised if PDE5 inhibitors are prescribed in combination with antihypertensive agents or agents with hypotensive properties. Patients receiving the combination should be advised to avoid rising abruptly from a sitting or recumbent position, especially following treatment initiation or a dosage increase, and to contact their doctor if they experience symptoms of hypotension such as dizziness, lightheadedness, fainting, or tachycardia.