Sildenafil (Viagra) and its congeners are potent inhibitors of phosphodiesterase (PDE), a type of enzyme that metabolizes cGMP. Losartan (Cozaar, the brand name for losartan potassium) is a potent and selective angiotensin II receptor antagonist that inhibits the action of angiotensin II in the blood and endothelial cells of blood vessels. The combination of these 2 drugs can raise the level of cGMP in the blood stream, which promotes vasodilation and cardiac output.
Since PDEs metabolize cGMP, it is possible that these drugs could interact, potentially resulting in adverse effects. There are 2 reports in the literature of patients taking both sildenafil and losartan experiencing adverse effects. We conducted a retrospective chart review of patients taking losartan who were prescribed sildenafil to see if there was an association between the 2 drugs. We report here 2 cases of acute renal failure in patients taking losartan and sildenafil.
Case 1
A 71-year-old white man with hypertension, diabetes, and hyperlipidemia was referred for a routine blood work-up because of recurrent pulmonary emboli for which he was taking warfarin sodium. His International Normalized Ratio (INR) was in the therapeutic range (2.0-3.0). He was also taking carvedilol (a combination of metoprolol and bisoprolol), aspirin, and digoxin. He denied taking any other medications or supplements. He had a history of chronic renal insufficiency, end-stage renal disease, and hemodialysis. Because he was also taking an angiotensin II receptor antagonist, he was started on sildenafil 50 mg 3 times a day with meals. The patient developed signs and symptoms of systemic hypotension, and the sildenafil was subsequently decreased to 25 mg 3 times a day. This response was followed by a decrease in the patient’s INR and a concomitant improvement in his clinical condition. Fourteen days after the patient was started on sildenafil, he developed signs and symptoms of acute renal failure, and his glomerular filtration rate (GFR) decreased by 52%. The patient had received a kidney transplant 6 years prior to admission, and he was currently on the kidney transplant list. Laboratory tests performed during the acute phase of the patient’s renal failure revealed creatinine (Cr) of 1.4 mg/dL and blood urea nitrogen (BUN) of 35 mg/dL. The patient’s medications were reviewed. Carvedilol was held, while the dose of the angiotensin II receptor antagonist was increased from 25 mg to 50 mg twice daily. After 2 days of treatment at the higher dose, the Cr level improved to 1.2 mg/dL, and the BUN decreased to 17 mg/dL. He was discharged on day 16 after admission with a follow-up appointment with his nephrologist scheduled 3 weeks later. The patient’s renal function improved significantly during the 30-day hospitalization. The patient was still undergoing treatment at the time of discharge, and his Cr and BUN were within normal limits (1.5 mg/dL and 16 mg/dL, respectively). Laboratory tests performed during his last follow-up visit before discharge revealed a Cr level of 1.5 mg/dL and a BUN level of 17 mg/dL. The patient had not yet taken his medications at the time of the visit.
Case 2
A 43-year-old African-American woman with hypertension was referred for a routine blood work-up because of renal failure. Her medical history was significant for diabetes mellitus, hypertension, and end-stage renal disease. She was on hemodialysis and had a transplanted kidney. She also underwent 2 cardiac surgeries. Because of her hypertension, she was taking valsartan (a combination of valsartan and amlodipine) and hydrochlorothiazide. She denied taking any other medications or supplements. She had a history of chronic renal insufficiency, end-stage renal disease, and hemodialysis. She was also taking carvedilol, aspirin, and digoxin. She had a routine blood glucose test, which was normal (77 mg/dL). Her INR was 2.7, and she was seen by the hematologist because of her anemia. Because she was also taking an angiotensin II receptor antagonist, she was started on sildenafil 50 mg 3 times a day with meals. Twenty-four hours after she started taking sildenafil, she complained of dizziness. Later that day, she developed shortness of breath and palpitations. Her blood pressure was within normal limits. The patient was seen by the hematologist, who noted that her pancytopenia (abnormalities in the numbers of red blood cells, white blood cells, and platelets) had improved, but her anemia remained. On day 4 of sildenafil treatment, her blood pressure was elevated. Her medications were reviewed. Carvedilol was held, and the dose of the angiotensin II receptor antagonist was increased to 100 mg twice daily. After 2 days of treatment at the higher dose, her blood pressure was within normal limits. Her Cr level improved to 1.9 mg/dL, and she became afebrile. The patient was discharged on day 7 after admission with a follow-up appointment with her nephrologist scheduled 3 weeks later.
We conducted a retrospective chart review of the medical records of 2 patients who were taking sildenafil and losartan at the time they developed acute renal failure. While taking sildenafil and losartan, both patients experienced significant decreases in their GFRs. We were unable to establish any direct cause-and-effect relationship between the 2 drugs. Both patients were taking multiple medications, which makes it difficult to tease out what role the sildenafil and losartan might have played in the development of their renal failure. The possibility of an adverse interaction between the 2 drugs has not been ruled out. Further studies are needed to establish the cause of the renal failure and whether there is any such adverse interaction. Until then, practitioners should be aware of the potential risk of this drug combination.