Sildenafil Nitroglycerin

Nitroglycerin should not be used within 24 hours of taking sildenafil or vardenafil or within 48 hours of taking tadalafil because of the potential for life-threatening hypotension. 

Orally active agents used in the treatment of ED are more affected by aging and disease processes than are those injected intracavernosally. In addition, alterations in hepatic metabolism and/or renal clearance in the elderly man (see Chapter 6) influence the frequency of appearance of adverse reactions between several coadministered drugs in the treatment of ED. For example, the concomitant use of sildenafil and nitroglycerin is contraindicated by cardiovascular complications. Also, the use of testosterone in the presence of androgen-dependent tumors may promote tumor growth. 

Pharmacological interactions are adverse effects that occur due to combined pharmacological activities, leading to exaggerated pharmacological effects. An example of pharmacological interactions is serious, sometimes fatal drop in blood pressure due to coadministration of nitroglycerin and sildenafil.3... 

Nitrovasodilators see Chapter 31) produce vasodilation by NO-dependent elevation of cychc GMP in vascular smooth muscle. The pharmacologic effects of sildenafil, tadalafil, and vardenafil result from inhibition of the type 5 cyclic nucleotide phosphodiesterase (PDE5) that hydrolyzes cyclic GMP to 5 GMP in the vasculature. Thus, coadministration of an NO donor e.g., nitroglycerin) with a PDE5 inhibitor can cause potentially catastrophic hypotension. 

The phosphodiesterase type-5 inhibitors potentiate the hypotensive effects of nitrates in a proportion of patients, which might re-suit in potentiaiiy serious hypotension or even precipitate myocardiai infarction. Therefore, the concurrent use of sildenafil, tadalafil or vardenafil with organic nitrates (glyceryl trinitrate (nitroglycerin), isosorbide dinitrate, isosorbide mononitrate, etc.) is contraindicated. The concurrent use of nicorandil and all phosphodiesterase type-5 inhibitors is also contraindicated. 

A postmarketing report from the FDA in the US for the period late March to July 1998 briefly lists 69 fatalities after taking sildenafil. These were mostly in middle-aged and elderly men (average age 64), 12 of whom had also taken glyceryl trinitrate (nitroglycerin) or a nitrate medication, but it is not clear what part (if any) the nitrates played in the deaths. ... 

The interaction between phosphodiesterase type-5 inhibitors and nitrates is established, clinically important, potentially serious and even possibly fatal. Sildenafil and organic nitrates of any form are contraindicated both for erectile dysfunction (within 24 hours of each other ) and for pulmonary hypertension because of the risk of precipitating serious hypotension, or even myocardial infarction. The ACC/AHA Expert consensus document provides a useful list of many of the organic nitrates available, whieh inelude glyeeryl trinitrate (nitroglycerin), isosorbide mononitrate, isosorbide dinitrate and illicit substances such as amyl nitrite. ... 

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