Lisinopril dosing

A 10-year-old boy developed hypotension and reduced alertness. His blood pressure was 56/24 mmHg and his heart rate 88/minute. He had a history of a hypoxic ischemic insult to the central nervous system, subsequent hypertension, and spastic quadriplegia. His blood pressure had been controlled for the last 10 months with lisinopril (dose not stated). Tizanidine had been added 1 week before admission for spasticity. Lisinopril and tizanidine were withdrawn and his blood pressure rose to 149/89 mmHg over the next day. He was discharged and lisinopril was restarted but not tizanidine. He had no further problems with hypotension. 

A report describes a 74-year-old woman with increased lithium levels of 2.3 mmol/L and symptoms of lithium toxicity, which were associated with several drugs including irbesartan, lisinopril, escitalopram, levomepro-mazine, furosemide and spironolactone. It was suggested that these drugs could have delayed lithium excretion or worsened neurotoxic effects. An increase in the lisinopril dose and the addition of irbesartan several weeks before admission may have contributed to the lithium toxicity. ... 

Lisinopril 2.5-5 mg once 20-40 mg once and after dose titration,... 

Lisinopril 2.5 to 5 mg initially target dose 10 to 20 mg once daily. 

All 10 ACE inhibitors available in the United States can be dosed once daily for hypertension except captopril, which is usually dosed two or three times daily. The absorption of captopril (but not enalapril or lisinopril) is reduced by 30% to 40% when given with food. 

Diuretic-treated patients Discontinue the diuretic, if possible, for 2 to 3 days before beginning therapy with lisinopril to reduce the likelihood of hypotension. If the diuretic cannot be discontinued, use an initial dose of 5 mg under medical supervision for at least 2 hours and until BP has stabilized for at least an additional hour. 

Acute Ml - In hemodynamically stable patients within 24 hours of the onset of symptoms of acute Ml, the first dose is 5 mg, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Continue dosing for 6 weeks. Patients with a low systolic BP (120 mm Hg or less) when treatment is started or during the first 3 days after the infarct should be given a lower 2.5 mg dose. If hypotension occurs (systolic BP 100 mm Hg or less), a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic BP less than 90 mm Hg for more than 1 hour), withdraw lisinopril. 

Captopril s pharmacokinetic parameters and dosing recommendations are set forth in Table 11-2. Peak concentrations of enalaprilat, the active metabolite of enalapril, occur 3-4 hours after dosing with enalapril. The half-life of enalaprilat is about 11 hours. Typical doses of enalapril are 10-20 mg once or twice daily. Lisinopril has a half-life of 12 hours. Doses of 10-80 mg once daily are effective in most patients. All of the ACE inhibitors except fosinopril and moexipril are eliminated primarily by the kidneys doses of these drugs should be reduced in patients with renal insufficiency. 

Lisinopril has a half-life of 12 hours. Doses of 10-80 mg once daily are effective in most patients. 

Phase I testing of lisinopril began in 1980. Single oral doses of 1.25 to 40 mg were given to normotensive volunteers, and at intervals thereafter pressor responses to intravenous angiotensin I were recorded. Lisinopril produced a noticeable inhibition of angiotensin I with oral doses as low as 1.25 mg, and efficacy persisted for 21 to 24 hours at the higher doses (133). 

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. 

If we are quite certain that ACE immobilized at the surface of the endotheliaf celfs is physiologicaliy more important than is the circulating enzyme (197), we do not know yet what is the relative importance of its bland C-terminal active sites. We do not know how they possibly affect the activity of each other. We do not know the physiological role of the N-acetyl SDKP, a relatively specific substrate of the N-terminal active site. We may still discover other natural substrates for endothelial and epithelial ACE. We do not fully understand the basis of differences in the various daily doses of ACE inhibitors as usually prescribed, from trandolapril 2 mg/day to lisinopril 80 mg/day, and the consequences of dose choices. 

Figure 6.3 Plot of the fraction of dose absorbed (in %) of various drugs as a function of the permeability estimates in the Caco-2 system. Key 1 D-glucose 2 verapamil 3 piroxicam 4 phenylalanine 5 cyclosporin 6 enalapril 7 cephalexim 8 losartan 9 lisinopril 10 amoxicillin 11 methyldopa 12 naproxen 13 an-tipyrine 14 desipramine 15 propanolol 16 amiloride 17 metoprolol 18 terbu-taline 19 mannitol 20 cimetidine 21 ranitidine 22 enalaprilate 23 atenolol 24 hydrochlorothiazide.

The information given here was sketchy and there was no information on the timing of blood samples relative to the dose of clozapine. Clozapine is metabolized by CYP1A2 and CYP3A4, but there is no evidence that lisinopril... 

Note that in the ATLAS trial no significant difference in mortality was found between low-dose (- 5 m day) and high-dose ( 35 mg/day) lisinopril therapy. 

Compliance. Multidrug therapy poses a substantial problem of compliance. Since treatment will be lifelong it is well worthwhile taking the trouble to find the most convenient regimen for each individual. A single daily dose would be ideal and to achieve this sustained-release formulations and fixed-dose combinations are used. Examples include Tenoretic (atenolol + chlortalidone), Tenif (atenolol + nifedipine) and Zestoretic (lisinopril + hydrochlorothiazide). 

The blood pressure of a 59-year-old man with hypertension and normal renal function rose when rofecoxib 25 mg/day was added to lisinopril 10 mg/day (from an average of 135/80-85 to 168/98 mmHg within 5 weeks). Four days after rofecoxib was withdrawn the blood pressure was 127/78 mmHg. Rechallenge with the same dose of rofecoxib produced the same effect and the blood pressure fell when the dosage of lisinopril was increased to 20 mg/day on continuous rofecoxib. The authors did not report on the course of renal function. 

Packer M, Poole-Whson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Ryden L, Thygesen K, Uretsky BF. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation 1999 100(23) 2312-18. 

An 82-year-old man with left ventricular dysfunction and gout had worsening renal function (33). He was taking lisinopril, furosemide, naproxen, allopurinol, and baclofen 20 mg tds. As no reason could be found for the use of baclofen the dose was halved and then stopped 10 days later. The next day he had visual hallucinations, confusion, and agitation, and required sedation with diazepam. He was afebrile, with normal inflammatory markers, and a CT scan of the brain showed only cerebral atrophy. Baclofen was reintroduced, with complete resolution of neuropsychiatric symptoms within 48 hours. 

A report from the Australian Drug Evaluation Committee has confirmed that dysgeusia (taste disturbance and taste loss) is more likely to complicate treatment with captopril than with other ACE inhibitors captopril accounted for more than half the cases of taste loss (3). Taste loss was dose-related, in that more than 90% of reports detailed a daily dose of 50 mg or more. Most cases recovered on withdrawal, although the sense of taste had not returned 7 months after withdrawal in one case, and in two of the reports there was associated anosmia. Although there was no significant difference between captopril and lisinopril... 

Massie BM, Armstrong PW, Qeland JG, Horowitz JD, Packer M, Poole-Wilson PA, Ryden L. Toleration of high doses of angiotensin-converting enzj me inhibitors in patients with chronic heart faUnre resnlts from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival Arch Intern Med 2001 161(2) 165-71. 

Carcinogenicity smdies carried out over years have not demonstrated any increased tumor incidence. No teratogenic effects have been documented in mice despite large chronic doses (e.g., 625 times the maximum daily dose of lisinopril on days 6-15 of gestation). 

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