Hypertension Knowledge Centre
Angiotensin II Antagonists
Tolerability and safety of eprosartan
Cumulative exposure to eprosartan worldwide is currently over 300 million patient days,64 and the clinical safety and adverse events profiles have been well established in clinical trials.7
Treatment-emergent adverse events
Eprosartan has been very well tolerated throughout the course of numerous controlled clinical studies, with a low incidence of treatment-emergent adverse events being reported, most of which were mild or transient, irrespective of dose.7 The frequency of adverse events is not affected by age, gender, race, or the frequency or duration of dosing.50 The incidence of impotence, oedema, flushing, fatigue and dizziness with eprosartan are similar to those with placebo.7 The low incidence of fatigue and dizziness means that patients can normally continue to drive or operate machinery whilst taking eprosartan therapy, provided they are aware that weariness or dizziness may occasionally arise during antihypertensive treatment.
Table 2 summarises the adverse events with eprosartan, as published in the international SmPC.65
Table 2: Frequency of adverse events with eprosartan. Data from eprosartan master Summary of Product Characteristics 65
| Nervous system disorders | Rare: headache, dizziness |
| Vascular disorders | Very rare: hypotension, including postural hypotension |
| Skin and subcutaneous tissue disorders |
Rare: skin reactions (rash, pruritus, urticaria) Very Rare: facial swelling, angio-oedema |
| General disorders and administration site reactions | Rare: asthenia |
Elderly patients
Pooled data from 15 studies of eprosartan (n=2,334) demonstrated that the overall incidence of adverse events reported in patients ?65 years was not significantly different from that reported in younger patients (figure 28).66 It was also shown that patients over 65 years of age did not have an exaggerated hypotensive response to eprosartan (dizziness, fatigue, injury, postural hypotension and syncope).
Figure 28. Most common therapy-related adverse events (>5%) by age in patients who received eprosartan. Adapted from 66
Low incidence of cough
A dry, non-productive and persistent cough is a common side effect of ACE inhibitors. Its incidence, reported to range from 15 to 35%, is probably related to the potentiation by ACE inhibition of bradykinin and other peptides.67 Cough has been shown to be significantly less frequent in patients receiving eprosartan than in those receiving enalapril.8,9
Elliott (1999), in a 26-week study involving 528 patients with mild-to-moderate essential hypertension, reported that the frequency of dry persistent cough with eprosartan was significantly lower than that with enalapril (1.5% versus 5.4%, respectively, p=0.018) (figure 29).8 This was also true for cough of any description (13.0% versus 22.0%, respectively).
Figure 29: Incidence of dry persistent cough (not due to upper respiratory tract infection) during the first 12 weeks of treatment with eprosartan or enalapril. Adapted from8
The lower incidence of dry persistent cough with eprosartan compared with enalapril has been confirmed in several other studies,9 including in the elderly41,52 and in black patients.53
Eprosartan has no significant effect on uric acid excretion
The AIIA losartan has been shown to increase urinary uric acid excretion and decrease serum urate levels in healthy volunteers,68 a property which is probably unrelated to AT1 antagonism.69 The difference in effect on uric acid metabolism between eprosartan and losartan has been demonstrated in a randomised, double-blind study in 60 outpatients with mild-to-moderate hypertension.49 Following a 2-3 week placebo run-in phase, patients received 4 weeks of active treatment with eprosartan (600mg once-daily) or losartan (50mg once-daily). Compared with baseline, after 4 weeks there was an increase in the ratio of uric acid to creatinine in the urine in the losartan group, but a slight fall in the ratio in the eprosatan group (+0.11 increase versus -0.04 decrease, respectively, p<0.01) (figure 30).
Figure 30: Change from baseline in the ratio of uric acid to creatinine in the urine after 4 weeks of treatment with eprosartan or losartan. Adapted from49
Well tolerated in combination with HCTZ
Böhm et al (2002) evaluated the safety and tolerability of eprosartan 100-800mg/day in combination with HCTZ in a meta-analysis of 17 studies involving 1,899 hypertensive patients and normotensive volunteers.70 Of the 17 studies included in this analysis four were controlled (patients received fixed doses), six were long-term open-label studies, four were controlled studies with HCTZ added to eprosartan therapy in non-responders, and three included healthy volunteers.
The various combinations of eprosartan and HCTZ were well tolerated in patients with hypertension (mild-to-moderate, isolated systolic and severe systolic hypertension). In the controlled studies, eprosartan/ HCTZ 600mg/12.5mg combination had a high completion rate, indicating good patient acceptance. In the controlled studies, headache, dizziness, myalgia and upper respiratory tract infections were the most frequently reported adverse events. Dizziness may be attributable to HCTZ and was more common in the patients receiving combination therapy.
Cautions/contraindications
Please see National Prescribing Information or Summary of Product Characteristics, as licence details may vary between countries.
Eprosartan is contraindicated in pregnancy, during breast feeding, and in patients hypersensitive to any component. Any sodium depletion or dehydration should be corrected before starting eprosartan. In patients with renal impairment, serum potassium should be monitored if taking concurrent drugs which increase potassium levels.
Safety
Eprosartan is not associated with any clinically significant changes in haematology and clinical chemistry parameters.50 Its use is associated with a very low incidence (<0.2%) of hyperkalaemia or hypokalaemia. Extensive monitoring during clinical trials suggests that eprosartan does not adversely affect heart rate or ECG parameters.
The incidence of adverse events in patients receiving aspirin or HMGCoA reductase inhibitors is similar to the incidence observed for the total study population. Metabolism of eprosartan does not involve the cytochrome P450 enzyme system, which reduces the potential for drug interactions; eprosartan is well tolerated when administered with other frequently prescribed drugs, including other antihypertensive agents, without any significant interaction liability.