Enalapril adverse effects

With the data included in the overview of Garg et al. (316), it is possible to calculate that 18 patients need to be treated for 90 days to avoid one death or one hospitalization for congestive heart failure (95% confidence interval [Cl] 16-23). This meta-analysis includes 32 trials with the ACE inhibitors captopril, enalapril, lisinopril, quinapril, ramipril, and perindopril. It is likely that high doses (for instance, lisinopril 35 mg daily) are more effective than low doses (lisinopril 5 mg daily) (302). Treating 30 patients for 4 years with a high dose of lisinopril (95% Cl 16-509) will avoid one hospitalization for cardiovascular reasons or one death in comparison with a low dose, without increasing the number of adverse effects requiring withdrawal from treatment. 

In the studies of left ventricular dysfunction (SOLVD), adverse effects related to the long-term use of enalapril have been thoroughly investigated (10). 

More trials during and after myocardial infarction have been pubhshed and subjected to meta-analysis (12). This very large database provides valuable information on the rate of the most common adverse effects. Of all trials of the effects of ACE inhibitors on mortality in acute myocardial infarction, only the CONSENSUS II trial did not show a positive effect. In this trial, enalaprUat was infused within 24 hours after the onset of symptoms, followed by oral enalapril. The reasons for the negative result of CONSENSUS II remain unresolved, but hypotension and a proischemic effect linked to a poorer prognosis have been suggested. 

Hepatic injury is a rare adverse effect of the ACE inhibitors (60,61). Both acute and chronic hepatitis and cholestatic jaundice can occur (62,63), as can cross-reactivity, as identified in a report involving enalapril and captopril (64). 

Enalapril has been specifically studied in patients who are resistant to other drugs and intolerant of captopril (99) and in patients with collagen vascular disease and renal disease known to be at high risk of adverse effects (100). In the first study (99), the major reasons for discontinuing captopril were a low white blood cell count, proteinuria, taste disturbance, and rash. In the vast majority of the 281 patients, these adverse effects did not recur during enalapril treatment. The main adverse events that warranted withdrawal of enalapril were impairment of renal function (5%), hypotension (2%), and rashes (2%). The authors noted that patients with angioedema should not be given alternative ACE inhibitors. 

Kostis JB, Shelton B, Gosselin G, Goulet C, Hood WB Jr, Kohn RM, Kubo SH, Schron E, Weiss MB, Willis PW 3rd, Young JB, Probstfield J. Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). SOLVD Investigators. Am Heart J 1996 131(2) 350-5. 

The authors suggested a synergistic effect between enalapril and mycophenolate. As leukopenia is the commonest clinically significant adverse effect of mycophenolate, the evidence in this case is inadequate to support this hypothesis, particularly in the absence of information on mycophenolate blood concentrations. 

In 12 healthy subjects probenecid 1 g twice daily for 5 days increased the AUC of a single 20-mg oral dose of enalapril and its active metabolite, enalaprilat by about 50%. The renal clearance of enalapril decreased by 12% A moderate increase in the hypotensive effects might be expected, but there do not appear to be any reports of adverse effects. 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

The problems of multiple prescribing in the elderly have been discussed in the context of a case of enalapril-associated dry cough misdiagnosed as pneumonia [34" ]. The prescribed antibiotics caused pseudomembranous colitis and an opioid-based syrup contributed to delirium. The authors drew attention to the effect of the prescribing cascade that can occur following the failure to identify an adverse drug reaction. 

---