Drug Interactions between Cialis and lisinopril

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of tadalafil, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MONITOR: Additive hypotensive effects may occur when phosphodiesterase-5 (PDE5) inhibitors such as tadalafil are used with alcohol, as both are mild systemic vasodilators. In clinical pharmacology studies, more subjects administered alcohol at a dose of 0.7 g/kg (equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male; consumed within 10 minutes in study subjects, providing blood alcohol levels of 0.08%) in combination with tadalafil 10 or 20 mg single doses had clinically significant decreases in blood pressure than with alcohol alone. There were reports of postural dizziness, and orthostatic hypotension was observed in some. When tadalafil 20 mg was administered with alcohol at a lower dose of 0.6 g/kg (equivalent to approximately 4 ounces of 80-proof vodka in an 80-kg male), orthostatic hypotension was not observed, dizziness occurred with similar frequency relative to alcohol alone, and the hypotensive effects of alcohol were not potentiated. Neither tadalafil nor alcohol affected the plasma concentrations of the other.

MANAGEMENT: Caution is recommended with concurrent consumption of large amounts of alcohol in patients taking tadalafil as it may increase the potential for orthostatic signs and symptoms, such as increase in heart rate, decrease in standing blood pressure, dizziness, and headache. It may also be appropriate to avoid consuming large amounts of grapefruit juice.

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

The use of these agents is contraindicated in patients with hereditary angioedema or a history of idiopathic angioedema. Patients with a history of angioedema unrelated to ACE inhibitors may be at increased risk of angioedema while receiving an ACE inhibitor. Patients should be advised to immediately report any signs or symptoms suggestive of angioedema (swelling of face, extremities, eyes, lips, or tongue, or difficulty swallowing or breathing) and to stop taking the medication until otherwise directed by their physician. Emergency therapy and/or measures to prevent airway obstruction are required for angioedema involving the tongue, glottis, or larynx. Treatment with ACE inhibitors should be discontinued permanently if angioedema develops in association with therapy.

ACE inhibitors may cause bone marrow suppression, rarely in uncomplicated individuals but more frequently in patients with renal impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma. Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, eosinophilia and thrombocytopenia have been reported, mostly with captopril. Therapy with ACE inhibitors should be administered cautiously in patients with preexisting blood dyscrasias or complications that may increase the risk of bone marrow depression during ACE inhibitor therapy. Monitoring of blood counts, particularly white blood cells, should be considered.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

ACE inhibitors can cause symptomatic hypotension, most often during the initiation of therapy and in patients who are volume- and/or sodium-depleted or treated for congestive heart failure (CHF). Therapy with ACE inhibitors should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if it was recently instituted; those on dietary salt restriction; those with severe or prolonged diarrhea or vomiting; and renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with ACE inhibitors, and the patient should be hemodynamically stable. If concomitant diuretics and/or dietary sodium restriction are employed, reducing or temporarily withholding the dosing of diuretics and/or liberalizing dietary sodium intake for 2 to 3 days in advance can help minimize the risk of severe hypotension in patients who are able to tolerate such adjustments. ACE inhibitors should also be used cautiously in patients in whom excessive hypotension may have serious consequences, such as patients with coronary or cerebrovascular insufficiency. Patients at risk for excessive hypotension should initiate ACE inhibitor therapy under very close medical supervision, and followed closely for the first 2 weeks of treatment and whenever the dosage of ACE inhibitor or diuretic is increased.

ACE inhibitors may cause bone marrow suppression, rarely in uncomplicated individuals but more frequently in patients with renal impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma. Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, eosinophilia and thrombocytopenia have been reported, mostly with captopril. Therapy with ACE inhibitors should be administered cautiously in patients with preexisting blood dyscrasias or complications that may increase the risk of bone marrow depression during ACE inhibitor therapy. Monitoring of blood counts, particularly white blood cells, should be considered.

ACE inhibitors can cause symptomatic hypotension, most often during the initiation of therapy and in patients who are volume- and/or sodium-depleted or treated for congestive heart failure (CHF). Therapy with ACE inhibitors should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if it was recently instituted; those on dietary salt restriction; those with severe or prolonged diarrhea or vomiting; and renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with ACE inhibitors, and the patient should be hemodynamically stable. If concomitant diuretics and/or dietary sodium restriction are employed, reducing or temporarily withholding the dosing of diuretics and/or liberalizing dietary sodium intake for 2 to 3 days in advance can help minimize the risk of severe hypotension in patients who are able to tolerate such adjustments. ACE inhibitors should also be used cautiously in patients in whom excessive hypotension may have serious consequences, such as patients with coronary or cerebrovascular insufficiency. Patients at risk for excessive hypotension should initiate ACE inhibitor therapy under very close medical supervision, and followed closely for the first 2 weeks of treatment and whenever the dosage of ACE inhibitor or diuretic is increased.

In patients with hyperkalemia, especially those associated with impaired renal function or congestive heart failure, ACE inhibitors may further raise serum potassium levels. Therapy with ACE inhibitors should be administered cautiously in patients with or predisposed to hyperkalemia, and serum potassium levels should be carefully monitored. Risk factors for the development of hyperkalemia during ACE inhibitor therapy include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes.

ACE inhibitors can cause symptomatic hypotension, most often during the initiation of therapy and in patients who are volume- and/or sodium-depleted or treated for congestive heart failure (CHF). Therapy with ACE inhibitors should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if it was recently instituted; those on dietary salt restriction; those with severe or prolonged diarrhea or vomiting; and renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with ACE inhibitors, and the patient should be hemodynamically stable. If concomitant diuretics and/or dietary sodium restriction are employed, reducing or temporarily withholding the dosing of diuretics and/or liberalizing dietary sodium intake for 2 to 3 days in advance can help minimize the risk of severe hypotension in patients who are able to tolerate such adjustments. ACE inhibitors should also be used cautiously in patients in whom excessive hypotension may have serious consequences, such as patients with coronary or cerebrovascular insufficiency. Patients at risk for excessive hypotension should initiate ACE inhibitor therapy under very close medical supervision, and followed closely for the first 2 weeks of treatment and whenever the dosage of ACE inhibitor or diuretic is increased.

Anaphylactoid reactions have been reported in patients undergoing hemodialysis with high-flux polyacrylonitrile membranes and treated concomitantly with an ACE inhibitor. The frequency and mechanism of this interaction have not been established, and it is not known whether the interaction occurs with other membrane types. Therapy with ACE inhibitors should be administered cautiously in patients requiring hemodialysis.

ACE inhibitors can cause symptomatic hypotension, most often during the initiation of therapy and in patients who are volume- and/or sodium-depleted or treated for congestive heart failure (CHF). Therapy with ACE inhibitors should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if it was recently instituted; those on dietary salt restriction; those with severe or prolonged diarrhea or vomiting; and renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with ACE inhibitors, and the patient should be hemodynamically stable. If concomitant diuretics and/or dietary sodium restriction are employed, reducing or temporarily withholding the dosing of diuretics and/or liberalizing dietary sodium intake for 2 to 3 days in advance can help minimize the risk of severe hypotension in patients who are able to tolerate such adjustments. ACE inhibitors should also be used cautiously in patients in whom excessive hypotension may have serious consequences, such as patients with coronary or cerebrovascular insufficiency. Patients at risk for excessive hypotension should initiate ACE inhibitor therapy under very close medical supervision, and followed closely for the first 2 weeks of treatment and whenever the dosage of ACE inhibitor or diuretic is increased.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

In patients with hyperkalemia, especially those associated with impaired renal function or congestive heart failure, ACE inhibitors may further raise serum potassium levels. Therapy with ACE inhibitors should be administered cautiously in patients with or predisposed to hyperkalemia, and serum potassium levels should be carefully monitored. Risk factors for the development of hyperkalemia during ACE inhibitor therapy include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes.

ACE inhibitors can cause symptomatic hypotension, most often during the initiation of therapy and in patients who are volume- and/or sodium-depleted or treated for congestive heart failure (CHF). Therapy with ACE inhibitors should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if it was recently instituted; those on dietary salt restriction; those with severe or prolonged diarrhea or vomiting; and renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with ACE inhibitors, and the patient should be hemodynamically stable. If concomitant diuretics and/or dietary sodium restriction are employed, reducing or temporarily withholding the dosing of diuretics and/or liberalizing dietary sodium intake for 2 to 3 days in advance can help minimize the risk of severe hypotension in patients who are able to tolerate such adjustments. ACE inhibitors should also be used cautiously in patients in whom excessive hypotension may have serious consequences, such as patients with coronary or cerebrovascular insufficiency. Patients at risk for excessive hypotension should initiate ACE inhibitor therapy under very close medical supervision, and followed closely for the first 2 weeks of treatment and whenever the dosage of ACE inhibitor or diuretic is increased.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

ACE inhibitors can cause symptomatic hypotension, most often during the initiation of therapy and in patients who are volume- and/or sodium-depleted or treated for congestive heart failure (CHF). Therapy with ACE inhibitors should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if it was recently instituted; those on dietary salt restriction; those with severe or prolonged diarrhea or vomiting; and renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with ACE inhibitors, and the patient should be hemodynamically stable. If concomitant diuretics and/or dietary sodium restriction are employed, reducing or temporarily withholding the dosing of diuretics and/or liberalizing dietary sodium intake for 2 to 3 days in advance can help minimize the risk of severe hypotension in patients who are able to tolerate such adjustments. ACE inhibitors should also be used cautiously in patients in whom excessive hypotension may have serious consequences, such as patients with coronary or cerebrovascular insufficiency. Patients at risk for excessive hypotension should initiate ACE inhibitor therapy under very close medical supervision, and followed closely for the first 2 weeks of treatment and whenever the dosage of ACE inhibitor or diuretic is increased.

Tadalafil tablet for the treatment of pulmonary arterial hypertension (PAH) should not be used in patients with pulmonary veno-occlusive disease (PVOD) as it may significantly worsen the cardiovascular status of these patients. If signs of pulmonary edema develop during therapy, the possibility of associated PVOD should be considered.

Tadalafil tablet for the treatment of pulmonary arterial hypertension (PAH) should not be used in patients with pulmonary veno-occlusive disease (PVOD) as it may significantly worsen the cardiovascular status of these patients. If signs of pulmonary edema develop during therapy, the possibility of associated PVOD should be considered.

The plasma clearance of phosphodiesterase-5 (PDE5) inhibitors may be decreased in patients with severe renal impairment, resulting in drug accumulation. Therapy with these agents should be avoided in patients with severe renal disease or on renal dialysis. Dose adjustments might be needed based on individual renal assessment and tolerability if used in these patients.

ACE inhibitors may cause bone marrow suppression, rarely in uncomplicated individuals but more frequently in patients with renal impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma. Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, eosinophilia and thrombocytopenia have been reported, mostly with captopril. Therapy with ACE inhibitors should be administered cautiously in patients with preexisting blood dyscrasias or complications that may increase the risk of bone marrow depression during ACE inhibitor therapy. Monitoring of blood counts, particularly white blood cells, should be considered.

In patients with hyperkalemia, especially those associated with impaired renal function or congestive heart failure, ACE inhibitors may further raise serum potassium levels. Therapy with ACE inhibitors should be administered cautiously in patients with or predisposed to hyperkalemia, and serum potassium levels should be carefully monitored. Risk factors for the development of hyperkalemia during ACE inhibitor therapy include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes.

ACE inhibitors can cause symptomatic hypotension, most often during the initiation of therapy and in patients who are volume- and/or sodium-depleted or treated for congestive heart failure (CHF). Therapy with ACE inhibitors should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if it was recently instituted; those on dietary salt restriction; those with severe or prolonged diarrhea or vomiting; and renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with ACE inhibitors, and the patient should be hemodynamically stable. If concomitant diuretics and/or dietary sodium restriction are employed, reducing or temporarily withholding the dosing of diuretics and/or liberalizing dietary sodium intake for 2 to 3 days in advance can help minimize the risk of severe hypotension in patients who are able to tolerate such adjustments. ACE inhibitors should also be used cautiously in patients in whom excessive hypotension may have serious consequences, such as patients with coronary or cerebrovascular insufficiency. Patients at risk for excessive hypotension should initiate ACE inhibitor therapy under very close medical supervision, and followed closely for the first 2 weeks of treatment and whenever the dosage of ACE inhibitor or diuretic is increased.

Alcohol consumption may intensify the pressure-lowering effects of mild vasodilators, such as phosphodiesterase 5 (PDE5) inhibitors. Therefore, patients that consume alcohol should be warned to limit alcohol intake while receiving these agents.

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours) have been reported during treatment with phosphodiesterase-5 (PDE 5) inhibitors. Priapism may result in penile tissue damage and permanent loss of potency if not treated promptly. These agents should be used cautiously in patients with conditions that may predispose them to priapism such as sickle cell anemia, multiple myeloma, or leukemia, and those with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). If an erection persists longer than 4 hours, the patient should seek immediate medical assistance.

Use of phosphodiesterase-5 (PDE5) inhibitors has been associated with sudden decrease or loss of hearing, which may be accompanied by tinnitus or dizziness. Patients with hearing problems should stop taking these agents and seek prompt medical care.

Phosphodiesterase 5 (PDE-5) inhibitors are cleared predominantly by hepatic metabolism. The pharmacokinetic disposition of these agents has not been assessed in patients with severe hepatic impairment. No dosage modification is recommended for patients with mild to moderate hepatic impairment, however, therapy with these agents should not be administered to patients with severe hepatic impairment. In patients with mild hepatic impairment a lower dose of these agents should be used as initial therapy.

Rarely, elevations of liver enzymes and/or serum bilirubin have occurred with the use of ACE inhibitors. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours) have been reported during treatment with phosphodiesterase-5 (PDE 5) inhibitors. Priapism may result in penile tissue damage and permanent loss of potency if not treated promptly. These agents should be used cautiously in patients with conditions that may predispose them to priapism such as sickle cell anemia, multiple myeloma, or leukemia, and those with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). If an erection persists longer than 4 hours, the patient should seek immediate medical assistance.

Tadalafil for the treatment of erectile dysfunction (ED) should be used with caution and only if the benefit outweighs the risk in patients with a history of non-arteritic anterior ischemic optic neuropathy (NAION) or with retinitis pigmentosa. Use of tadalafil for the treatment of pulmonary arterial hypertension is not recommended in patients with retinitis pigmentosa. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking tadalafil; patients taking tadalafil for ED should immediately stop treatment. Most patients who developed NAION during therapy with tadalafil had underlying anatomic or vascular risk factors, including low cup to disc ratio ("crowded disc").

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours) have been reported during treatment with phosphodiesterase-5 (PDE 5) inhibitors. Priapism may result in penile tissue damage and permanent loss of potency if not treated promptly. These agents should be used cautiously in patients with conditions that may predispose them to priapism such as sickle cell anemia, multiple myeloma, or leukemia, and those with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). If an erection persists longer than 4 hours, the patient should seek immediate medical assistance.

With the exception of fosinopril, ACE inhibitors (and/or their active metabolites in some cases) are primarily eliminated by the kidney and may accumulate in patients with renal impairment. ACE inhibitors can also worsen renal function in some patients by blocking the effect of angiotensin II-mediated efferent arteriolar vasoconstriction, thereby decreasing glomerular filtration. Therapy with ACE inhibitors should be administered cautiously in patients with preexisting renal dysfunction, particularly those with renovascular disease. Patients with moderate to severe renal impairment usually require lower or less frequent doses and smaller increments in dose. In addition, a dosage reduction or discontinuation of any concomitantly administered diuretics may be helpful. Fosinopril probably does not require dosage adjustments unless hepatic function is also significantly impaired.

In patients with bilateral renal artery stenosis or renal artery stenosis in a solitary kidney, ACE inhibitors may reduce renal perfusion to a critically low level. Renal function should be monitored closely for the first few weeks of therapy.

Tadalafil for the treatment of erectile dysfunction (ED) should be used with caution and only if the benefit outweighs the risk in patients with a history of non-arteritic anterior ischemic optic neuropathy (NAION) or with retinitis pigmentosa. Use of tadalafil for the treatment of pulmonary arterial hypertension is not recommended in patients with retinitis pigmentosa. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking tadalafil; patients taking tadalafil for ED should immediately stop treatment. Most patients who developed NAION during therapy with tadalafil had underlying anatomic or vascular risk factors, including low cup to disc ratio ("crowded disc").

Phosphodiesterase-5 (PDE5) inhibitors have been associated with transient impairment of color discrimination (blue/green) and blue- or color-tinged vision. These agents also inhibit phosphodiesterase-6 (PDE6), to a much lesser extent, which is involved in phototransduction in the retina. There are no controlled clinical data on the safety in patients with retinitis pigmentosa, a minority of whom may have genetic disorders of retinal phosphodiesterases. Therapy with these agents should be avoided in such patients.

The use of phosphodiesterase 5 (PDE-5) inhibitors has been associated with seizures. Therapy with these agents should be administered cautiously in patients with preexisting seizure disorders.

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours) have been reported during treatment with phosphodiesterase-5 (PDE 5) inhibitors. Priapism may result in penile tissue damage and permanent loss of potency if not treated promptly. These agents should be used cautiously in patients with conditions that may predispose them to priapism such as sickle cell anemia, multiple myeloma, or leukemia, and those with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). If an erection persists longer than 4 hours, the patient should seek immediate medical assistance.

Use of phosphodiesterase-5 (PDE5) inhibitors has been associated with sudden decrease or loss of hearing, which may be accompanied by tinnitus or dizziness. Patients with hearing problems should stop taking these agents and seek prompt medical care.

Tadalafil for the treatment of erectile dysfunction (ED) should be used with caution and only if the benefit outweighs the risk in patients with a history of non-arteritic anterior ischemic optic neuropathy (NAION) or with retinitis pigmentosa. Use of tadalafil for the treatment of pulmonary arterial hypertension is not recommended in patients with retinitis pigmentosa. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking tadalafil; patients taking tadalafil for ED should immediately stop treatment. Most patients who developed NAION during therapy with tadalafil had underlying anatomic or vascular risk factors, including low cup to disc ratio ("crowded disc").