Eprosartan: A Comprehensive Pharmacological and Clinical Review

1. Introduction

Eprosartan is an antihypertensive medication belonging to the Angiotensin II Receptor Blocker (ARB) class of drugs.[1] It functions primarily as a selective antagonist of the Angiotensin II Type 1 (AT1) receptor subtype.[3] Its main therapeutic application is in the management of essential hypertension.[6]

Chemically, eprosartan possesses a unique structure that distinguishes it from many other ARBs. It is characterized as a non-biphenyl, non-tetrazole compound, belonging to the chemical classes of imidazoles and thiophenes.[1] This structural distinction may contribute to some of its specific pharmacological properties.

The mechanism of action involves more than simple receptor blockade. Eprosartan inhibits the physiological effects mediated by angiotensin II binding to the AT1 receptor, leading to vasodilation and reduced aldosterone secretion.[1] Furthermore, some evidence suggests a dual mechanism involving the inhibition of norepinephrine release from sympathetic nerve endings, potentially via presynaptic AT1 receptor blockade, which may contribute further to its blood pressure-lowering effect.[1]

Eprosartan was originally developed by SmithKline Beecham (now part of GSK) [10] and received initial FDA approval in the United States in 1997 under the brand name Teveten.[11] However, it is important to note that both the brand name (Teveten, Teveten HCT) and generic formulations of eprosartan have been discontinued in the United States market.[13] This discontinuation was reportedly due to business reasons and not related to concerns about the drug's safety or efficacy.[15] This significantly impacts its current clinical availability and utility for practitioners in the US, rendering its study more relevant for understanding ARB pharmacology, historical context, or for potential use in regions where it might still be available.

This report aims to provide a comprehensive overview of eprosartan, synthesizing available data on its chemical and physical properties, mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, approved and potential indications, dosage, administration, safety profile, regulatory status, and market availability.

2. Chemical and Physical Properties

Eprosartan is identified by several names and codes across different databases and regulatory agencies.

• Drug Name: Eprosartan [1]
• Brand Names: Teveten (discontinued US/EU) [2], Teveten HCT (combination product, discontinued US) [6], Eprozar [12], Navixen.[10]
• DrugBank ID: DB00876 [1]
• CAS Number: 133040-01-4 [1]
• Other Identifiers: UNII: 2KH13Z0S0Y [1], ChEBI: CHEBI:4814 [1], ChEMBL: CHEMBL813 [1], KEGG: D04040 [1], PubChem CID: 5281037 [17], ATC codes: C09CA02 (eprosartan), C09DA02 (eprosartan and diuretics).[6]

Its chemical structure incorporates imidazole and thiophene moieties.[1] The IUPAC name is (E)-4-({2-Butyl-5-[2-carboxy-3-(thiophen-2-yl)prop-1-en-1-yl]-1H-imidazol-1-yl}methyl)benzoic acid.[17]

Table 1: Key Chemical and Physical Properties of Eprosartan

Property	Value	Reference(s)
Chemical Formula	C23​H24​N2​O4​S	5
Molecular Weight (Base)	Average: 424.51-424.52 g/mol<br>Monoisotopic: 424.145678 g/mol	5
Molecular Weight (Mesylate)	520.625 g/mol	3
CAS Number	133040-01-4	1
Appearance	Solid; White to off-white crystalline powder; Crystals from methanol	1
Melting Point (Base)	260-261 °C	1
Melting Point (Mesylate)	248-250 °C	1
Solubility (Water)	Base: Poorly soluble, Low (8.66e-03 g/L or 0.00866 mg/mL)<br>Mesylate: Insoluble	1
Solubility (Ethanol)	Mesylate: Freely soluble	1
LogP (Octanol/Water Partition)	3.57 - 4.74 (predicted values vary by method/source)	1
Stability	Stable under recommended storage conditions	1

The base form of eprosartan exhibits low aqueous solubility, a factor contributing to its limited oral bioavailability.[30] The mesylate salt form (eprosartan mesylate), commonly used in pharmaceutical formulations [3], is described as insoluble in water but freely soluble in ethanol.[1] LogP values, which indicate lipophilicity, are predicted to be relatively high (ranging from approximately 3.6 to 4.7 depending on the calculation method), suggesting good membrane permeability potential, consistent with its classification as a Biopharmaceutics Classification System (BCS) Class II drug (low solubility, high permeability).[30]

3. Mechanism of Action

Eprosartan exerts its antihypertensive effect primarily through selective antagonism of the Angiotensin II Type 1 (AT1) receptor.[1] Angiotensin II (Ang II) is a potent vasoconstrictor and the principal pressor agent of the Renin-Angiotensin-Aldosterone System (RAAS).[3] Besides vasoconstriction, Ang II stimulates aldosterone synthesis and secretion from the adrenal cortex, enhances cardiac contractility, promotes renal sodium resorption, increases sympathetic nervous system activity, and stimulates smooth muscle cell growth.[3]

Eprosartan competitively and reversibly blocks the binding of Ang II to AT1 receptors located in various tissues, including vascular smooth muscle and the adrenal glands.[1] This blockade inhibits the downstream effects of Ang II, namely vasoconstriction and aldosterone secretion.[3] The result is relaxation of vascular smooth muscle, leading to vasodilation and a decrease in peripheral vascular resistance, which lowers blood pressure.[1] Inhibition of aldosterone secretion contributes to reduced sodium and water retention.

Eprosartan demonstrates high affinity and selectivity for the AT1 receptor, with an affinity reported to be over 1,000 times greater than for the Angiotensin II Type 2 (AT2) receptor.[3] The AT2 receptor is not currently known to be associated with cardiovascular homeostasis.[3] Eprosartan acts purely as an antagonist, lacking any partial agonist activity at the AT1 receptor.[3] Furthermore, it exhibits inverse agonist properties, meaning it can reduce the basal activity of the AT1 receptor even in the absence of Ang II, potentially stabilizing the receptor in inactive conformations.[9]

Blockade of the AT1 receptor interrupts the negative feedback loop of Ang II on renin secretion. Consequently, plasma renin activity and circulating Ang II levels may increase; however, these increases do not override the antihypertensive effect of eprosartan's receptor blockade.[3]

Some evidence points towards a potential "dual action" for eprosartan.[1] In addition to postsynaptic AT1 receptor blockade, eprosartan may also inhibit sympathetically stimulated norepinephrine release by blocking presynaptic AT1 receptors on sympathetic neurons.[5] This inhibition of sympathetic outflow could provide an additional mechanism for blood pressure reduction beyond direct vasodilation.[1] While the primary mechanism remains AT1 antagonism, this potential sympathetic modulation might contribute to its overall hemodynamic profile and differentiate it subtly from other ARBs.

A key distinction between ARBs like eprosartan and Angiotensin-Converting Enzyme (ACE) inhibitors lies in their interaction with bradykinin. ACE (also known as kininase II) is responsible for degrading bradykinin, a substance implicated in the cough reflex.[3] Eprosartan does not inhibit ACE/kininase II and therefore does not interfere with bradykinin metabolism.[3] This fundamental mechanistic difference is widely accepted as the reason for the significantly lower incidence of dry cough observed with ARBs compared to ACE inhibitors, a major tolerability advantage.[17]

4. Pharmacokinetics (PK)

The pharmacokinetic profile of eprosartan is characterized by low oral bioavailability, high protein binding, minimal metabolism, and elimination primarily via biliary excretion.

Absorption: Eprosartan exhibits low and somewhat variable oral absorption. The absolute bioavailability following a 300 mg oral dose is approximately 13%.[3] This limited bioavailability is likely due to its poor aqueous solubility and dissolution rate [30], and potentially incomplete absorption across the gastrointestinal tract.[41] Peak plasma concentrations (Cmax) are typically achieved within 1 to 2 hours after oral administration in the fasted state.[3] Co-administration with food delays the rate of absorption and can cause variable changes (generally less than 25%) in Cmax and the Area Under the Curve (AUC), but these effects are not considered clinically significant.[3] Consequently, eprosartan can be administered with or without food.[4] Over the dosage range of 100 mg to 800 mg, plasma concentrations increase in a manner slightly less than proportional to the dose.[3] The low bioavailability necessitates relatively high oral doses (e.g., 400-800 mg) to achieve therapeutic effects compared to some other ARBs with better absorption characteristics.

Distribution: Eprosartan is extensively bound to plasma proteins, with approximately 98% binding observed, which remains constant across the therapeutic concentration range.[3] Protein binding is not significantly affected by mild-to-moderate renal impairment or hepatic dysfunction.[29] However, in patients with severe renal impairment, the unbound fraction of eprosartan in plasma increases significantly (approximately twofold).[29]

There is a notable discrepancy in the reported Volume of Distribution (Vd). Some earlier reviews or studies cite a relatively small Vd of approximately 13 Litres [30], suggesting limited distribution outside the plasma compartment. However, later FDA labels, based on population pharmacokinetic (PopPK) analyses from Phase 3 trials, report a large population mean steady-state volume of distribution (Vss/F) of 308 Litres.[3] This larger Vss/F value, which accounts for bioavailability (F) and reflects distribution at steady state, suggests extensive distribution into tissues, despite the high plasma protein binding. This discrepancy likely arises from differences in calculation methods (e.g., initial Vd vs. steady-state Vd from PopPK) and the phases of drug distribution being measured. The larger Vss/F indicates significant tissue uptake or binding.

Metabolism: Eprosartan undergoes minimal metabolism in the body.[17] It is primarily eliminated as the unchanged parent compound.[3] A minor metabolic pathway involves glucuronidation, with less than 2% of an oral dose being excreted in the urine as an acyl glucuronide metabolite.[3] No pharmacologically active metabolites have been identified.[3] Crucially, eprosartan is not metabolized by the cytochrome P450 (CYP) enzyme system and does not inhibit human CYP enzymes in vitro.[3] This lack of involvement with the CYP system significantly reduces the potential for metabolic drug-drug interactions, a notable advantage, especially in patients receiving multiple medications (polypharmacy), which is common in elderly populations or those with comorbidities.[35]

Elimination: Eprosartan is eliminated from the body through both biliary and renal routes, with biliary excretion being the predominant pathway.[3] Following an intravenous dose, approximately 61% of the administered radioactivity is recovered in the feces (via bile) and 37% in the urine.[4] After an oral dose, reflecting the primary route of elimination for the absorbed fraction plus unabsorbed drug, about 90% is recovered in feces and only about 7% in urine.[3] Hepatic elimination accounts for approximately 10% of systemic clearance.[9]

Similar to the Vd, there is a discrepancy in the reported elimination half-life (t1/2). Many sources, often citing earlier studies or single-dose data, report a terminal elimination half-life of 5 to 9 hours after oral administration.[5] However, FDA prescribing information based on multiple-dose studies indicates a longer mean terminal elimination half-life of approximately 20 hours.[3] This difference might reflect the pharmacokinetic behavior after reaching steady state, where slower elimination from tissue compartments or potential enterohepatic recirculation could contribute to a longer apparent half-life compared to the initial decline phase after a single dose. The longer effective duration suggested by the 20-hour half-life aligns better with the observed 24-hour pharmacodynamic effect (see Section 5).

Plasma clearance is relatively low, reported as approximately 130 mL/min.[40] Population PK analysis estimated a mean oral clearance (CL/F) of 48.5 L/hr for an average 60-year-old patient, which decreases linearly with increasing age.[3] There is no evidence of significant drug accumulation with chronic administration.[4] Eprosartan is poorly removed by hemodialysis.[3]

Special Populations:

• Elderly: Systemic exposure (AUC and Cmax) is approximately doubled in elderly individuals (e.g., 68-78 years) compared to young adults (e.g., 20-39 years) [29], likely due to increased bioavailability and decreased clearance with age.[34] Despite this, no initial dose adjustment is typically required due to the drug's good safety profile in this population.[3]
• Renal Impairment: Moderate to severe renal impairment (creatinine clearance [CrCl] < 60 mL/min) leads to a significant increase in systemic exposure (AUC increased by 70-90%, Cmax by 30-50%) and an increase in the unbound fraction.[29] Therefore, a maximum daily dose of 600 mg is recommended for these patients.[3] Caution is advised for CrCl < 30 mL/min or patients on dialysis.[31]
• Hepatic Impairment: Mild to moderate hepatic impairment results in an approximate 40% increase in AUC, with no significant change in Cmax.[34] No initial dose adjustment is generally needed, but experience is limited, and caution should be exercised.[3] Eprosartan is contraindicated in severe hepatic impairment according to European labeling, reflecting the importance of biliary excretion.[7]
• Gender and Race: Pharmacokinetics are not significantly influenced by gender or race.[3]

Table 2: Summary of Eprosartan Pharmacokinetic Parameters

Parameter	Value / Description	Reference(s)
Absolute Bioavailability (%)	~13%	3
Tmax (Time to Peak Conc.)	1-2 hours (fasted)	3
Food Effect	Delays absorption; minor (<25%) variable changes in Cmax/AUC; clinically unimportant. Can take with/without food.	3
Protein Binding (%)	~98% (high); constant over therapeutic range	3
Volume of Distribution (Vd)	Discrepancy: ~13 L (earlier reports/initial Vd?) vs. 308 L (PopPK Vss/F, suggests extensive tissue distribution)	30 vs 3
Metabolism	Minimal; Primarily unchanged drug. <2% as inactive acyl glucuronide. Not metabolized by CYP450 enzymes. No active metabolites.	3
Elimination Route (%)	Primarily biliary/fecal (~90% oral dose); Renal (~7% oral dose)	3
Elimination Half-life (t1/2)	Discrepancy: 5-9 hours (single dose terminal phase?) vs. ~20 hours (multiple dose terminal phase?)	5 vs 3
Clearance	Low plasma clearance (~130 mL/min); PopPK CL/F ~48.5 L/hr (decreases with age)	40 vs 3
Effect of Renal Impairment	Increased AUC/Cmax in moderate/severe (CrCl <60 mL/min). Max dose 600 mg/day recommended.	3
Effect of Hepatic Impairment	Increased AUC (~40%) in mild/moderate. No initial dose adjustment but use caution. Contraindicated in severe (EMA).	3

5. Pharmacodynamics (PD)

The pharmacodynamic effects of eprosartan are primarily related to the consequences of AT1 receptor blockade within the RAAS.

Primary Effect: Eprosartan effectively inhibits the physiological actions of Ang II. Clinical studies using Ang II infusions have demonstrated that eprosartan blocks the expected vasopressor (blood pressure raising), renal vasoconstrictive, and aldosterone secretory responses.[3] Complete inhibition of these effects is generally observed with single oral doses of 350 mg or higher.[3] The primary clinical outcome is a reduction in systemic blood pressure.[1]

Onset and Duration of Action: The onset of blood pressure reduction is typically observed within 1 to 2 hours following oral administration.[4] Despite the variable reported plasma half-life (5-9 hours single dose vs. 20 hours multi-dose), eprosartan provides sustained blood pressure control over a 24-hour period with either once-daily or twice-daily dosing regimens.[3] Studies using ambulatory blood pressure monitoring confirmed significant BP reduction throughout the 24-hour dosing interval.[36] A single 350 mg dose can inhibit the pressor response to Ang II infusion by approximately 100% at its peak effect, with roughly 30% inhibition still present after 24 hours.[3] Achieving the maximal blood pressure response to a given dose may take 2 to 3 weeks of continuous therapy.[3] This dissociation between the shorter initial plasma half-life and the sustained 24-hour pharmacodynamic effect supports the clinical utility of once-daily dosing and suggests that tissue receptor binding or the longer multi-dose elimination phase may be more relevant for duration of action than initial plasma drug levels.

Hemodynamic Effects: Eprosartan lowers blood pressure primarily by reducing peripheral vascular resistance. This reduction is generally achieved without causing a significant reflex increase in heart rate.[31] While generally well-tolerated regarding postural changes, symptomatic hypotension (dizziness, lightheadedness, fainting upon standing) can occur, particularly in patients who are volume- or salt-depleted.[3]

Renal Effects: Eprosartan has demonstrated effects on renal hemodynamics. It increases mean effective renal plasma flow (ERPF) in both salt-replete and salt-restricted healthy individuals, with the effect appearing to plateau between the 200 mg and 400 mg doses.[4] Importantly, therapeutic doses of eprosartan do not appear to adversely affect the glomerular filtration rate (GFR) in hypertensive patients or those with pre-existing renal insufficiency.[3] Furthermore, it does not alter the fractional excretion of sodium or potassium in these patient groups [34] and does not significantly impact urinary uric acid excretion.[31]

Metabolic Effects: Eprosartan exhibits a neutral metabolic profile. Clinical trials have shown it does not significantly affect levels of fasting triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, or fasting glucose.[3] This is an advantage, particularly for hypertensive patients with coexisting metabolic conditions like diabetes or dyslipidemia, where other antihypertensive classes might negatively impact metabolic control. Unlike some other ARBs (e.g., telmisartan), eprosartan does not significantly activate peroxisome proliferator-activated receptor gamma (PPAR-γ), and therefore lacks intrinsic insulin-sensitizing properties.[9]

Endocrine Effects: As expected from AT1 receptor blockade, chronic eprosartan treatment leads to a compensatory increase in plasma renin activity and circulating Ang II levels due to the loss of negative feedback inhibition.[3] However, plasma aldosterone concentrations and serum potassium levels generally remain unchanged under normal conditions.[3]

Rebound Effect: Discontinuation of eprosartan therapy is not associated with a rapid rebound increase in blood pressure.[3]

6. Clinical Efficacy and Trials

Clinical trials have established the efficacy and safety of eprosartan in the management of hypertension, comparing it against placebo and other active antihypertensive agents.

6.1. Efficacy in Hypertension (Monotherapy & Combination):

Eprosartan effectively lowers both systolic and diastolic blood pressure in patients with essential hypertension across a range of severities (mild, moderate, severe).1 It can be used as monotherapy or effectively combined with other classes of antihypertensive drugs, such as thiazide diuretics (e.g., hydrochlorothiazide - HCTZ) and calcium channel blockers (e.g., nifedipine), to achieve additive blood pressure lowering.1 The fixed-dose combination product Teveten HCT (eprosartan/HCTZ) was developed based on this additive effect.3

6.2. Comparative Clinical Trials:

• vs. Placebo: Multiple randomized, controlled trials demonstrated that eprosartan (alone or with HCTZ) provides statistically significant and clinically meaningful reductions in blood pressure compared to placebo.[9] The tolerability profile of eprosartan was consistently shown to be similar to that of placebo.[9]
• vs. Enalapril (ACE Inhibitor): Comparative trials indicated that eprosartan produces blood pressure lowering effects comparable to those of the ACE inhibitor enalapril when administered at similar dosages.[9] A key finding from these comparisons was the superior tolerability of eprosartan, specifically a significantly lower incidence of persistent dry cough, a common side effect associated with ACE inhibitors.[9] One study in patients with severe hypertension suggested that eprosartan administered twice daily might be more effective at reducing systolic blood pressure than once-daily enalapril.[9]
• vs. Nitrendipine (Calcium Channel Blocker) - MOSES Study: The Morbidity and Mortality after Stroke, Eprosartan compared with Nitrendipine for Secondary prevention (MOSES) trial was a significant secondary prevention study in hypertensive patients with a history of cerebrovascular events.[9] Patients were randomized to eprosartan or nitrendipine. Despite achieving similar levels of blood pressure control in both groups, the eprosartan group experienced significantly fewer events contributing to the primary composite endpoint (all-cause mortality, all cardiovascular events, and all cerebrovascular events, including recurrent events).[9] This finding suggests that eprosartan may confer cerebrovascular protective benefits beyond those attributable solely to blood pressure reduction, a potentially important distinction for patients at high risk of stroke recurrence.
• vs. Other ARBs: Limited direct comparative data were found in the provided snippets, but some reviews mention studies suggesting eprosartan showed greater efficacy than losartan in managing coagulation abnormalities and peripheral resistance, and a greater reduction in vascular resistance during stress tests compared to valsartan.[9]

6.3. Studies in Specific Populations/Outcomes:

• OSCAR Study (Cognitive Function): The Observational Study on Cognitive function And Systolic blood pressure Reduction (OSCAR) was a large, multi-national observational study involving over 20,000 patients aged 50 years or older with newly diagnosed hypertension.[9] Treatment based on eprosartan resulted in significant blood pressure reduction over 6 months. Notably, the study also observed a modest but statistically significant improvement in cognitive function, as measured by the Mini-Mental State Examination (MMSE) score, particularly in patients achieving better systolic blood pressure control.[9] While observational data cannot establish causality, these findings generate a hypothesis regarding potential cognitive benefits associated with eprosartan-based therapy in this population.
• Type 2 Diabetes Mellitus (T2DM): Eprosartan has been shown to effectively control blood pressure in hypertensive patients who also have T2DM.[9] A clinical trial (NCT00160160) specifically compared the combination of Eprosartan/HCTZ versus Enalapril/HCTZ in hypertensive patients with T2DM.[52] It is critical to note, however, that current guidelines generally advise against the dual blockade of the RAAS (e.g., combining an ARB with an ACE inhibitor), particularly in patients with diabetic nephropathy, due to increased risks of adverse events without clear additional benefit.[31]
• Healthy Volunteers: Studies have assessed the effects of eprosartan on hormonal profiles and kidney function in healthy individuals (e.g., NCT00409903).[55]
• Essential Hypertension Trials: Specific trials focused on essential hypertension include Phase 3 comparisons (e.g., NCT01631227 comparing eprosartan vs. eprosartan mesylate) [56] and Phase 4 post-marketing studies (e.g., NCT00438945 assessing hormone/kidney effects in hypertensives).[57]

6.4. Dosing Regimen Studies:

• Once vs. Twice Daily: A key multinational study directly compared the efficacy and tolerance of once-daily (400-800 mg total) versus twice-daily (200-400 mg BID total) eprosartan regimens in patients with mild-to-moderate hypertension.[50] The study found no significant difference between the two regimens in terms of blood pressure reduction or overall tolerability. Both regimens were significantly more effective than placebo.[50] This supports the convenience of once-daily dosing for improving patient compliance.[50] However, prescribing information acknowledges that if the antihypertensive effect measured at trough (just before the next dose) is inadequate with once-daily dosing, switching to a twice-daily regimen (at the same total daily dose) or increasing the dose may provide a better response.[3] This flexibility might account for inter-patient pharmacokinetic variability or the need to ensure sustained receptor blockade throughout the entire 24-hour interval.
• 24-hour BP Control: A dedicated study using ambulatory blood pressure monitoring evaluated the 24-hour efficacy of eprosartan 600 mg once daily versus 1200 mg once daily.[36] Both doses significantly reduced blood pressure over the entire 24-hour period compared to placebo.[45] Importantly, there was no statistically significant difference in blood pressure reduction between the 600 mg and 1200 mg doses.[45] This led to the conclusion that 600 mg once daily is likely the optimal dose, as the higher 1200 mg dose did not offer additional antihypertensive benefit.[36]

Table 3: Summary of Key Eprosartan Clinical Trials

Trial Name/Identifier	Patient Population	Comparator(s)	Key Endpoints	Key Outcomes/Findings	Reference(s)
MOSES	Hypertensive patients with prior cerebrovascular event	Nitrendipine	Primary: Composite of all-cause mortality, all CV & cerebrovascular events	Eprosartan showed superior outcomes despite similar BP reduction, suggesting additional cerebrovascular protection.	9
OSCAR	≥50 years, newly diagnosed hypertension	Observational	BP reduction, Cognitive function (MMSE)	Eprosartan-based therapy reduced BP significantly and was associated with modest improvement in MMSE score over 6-12 months.	9
Various Trials	Mild-to-severe Hypertension	Enalapril	BP reduction, Tolerability (cough)	Eprosartan had similar BP-lowering efficacy but significantly lower incidence of cough. One study suggested better SBP reduction with Eprosartan BID vs Enalapril OD in severe hypertension.	9
Various Trials	Mild-to-moderate Hypertension	Placebo	BP reduction, Tolerability	Eprosartan significantly reduced BP compared to placebo with a similar tolerability profile.	9
Dosing Regimen Study	Mild-to-moderate Hypertension	Eprosartan OD vs BID	BP reduction, Tolerability	No significant difference in efficacy or tolerance between once-daily and twice-daily dosing; both superior to placebo. Supports OD dosing convenience.	50
24hr ABPM Study	Systemic Hypertension	Placebo, Epro 1200mg OD	24-hour BP change, Trough BP change	Eprosartan 600mg OD significantly reduced BP over 24 hours. No significant difference between 600mg and 1200mg doses, suggesting 600mg OD is optimal dose.	36
NCT00160160	Hypertensives with Type II Diabetes	Enalapril/HCTZ	BP reduction	Compared Eprosartan/HCTZ vs Enalapril/HCTZ combination therapy. (Specific outcome not provided in snippet).	52

7. Therapeutic Indications and Usage

The approved indications for eprosartan differ slightly between regulatory agencies, and potential uses associated with the ARB class are not necessarily approved for eprosartan itself.

7.1. Approved Indications:

• United States (FDA): Eprosartan (Teveten) was approved for the treatment of hypertension. It could be used as monotherapy or in combination with other antihypertensive agents, such as diuretics and calcium channel blockers.[1] The fixed-dose combination product, Teveten HCT (eprosartan/hydrochlorothiazide), was also indicated for hypertension but was not recommended for initiating therapy.[3] Crucially, all eprosartan-containing products (brand and generic) are currently discontinued and unavailable in the US market.[13]
• Europe (EMA): Eprosartan is indicated for the treatment of essential hypertension in adults.[7]

7.2. Other Investigated or Mentioned Uses (Likely Off-Label):

While eprosartan's approved indication is limited to hypertension, other conditions where RAAS inhibition is beneficial are sometimes associated with the ARB class or mentioned in relation to eprosartan, though these are generally considered off-label uses for this specific drug:

• Diabetic Nephropathy: ARBs as a class are used to slow the progression of kidney damage in patients with diabetes (diabetic nephropathy).[2] Some sources mention that similar dosing regimens as used for hypertension have been employed for eprosartan in this context.[46] However, this is not an FDA or EMA-approved indication specifically for eprosartan. Furthermore, regulatory bodies strongly advise against combining ARBs with ACE inhibitors, particularly in patients with diabetic nephropathy, due to increased risks without proven benefit.[31]
• Congestive Heart Failure (CHF): ARBs are established treatments for CHF, often used as an alternative for patients who cannot tolerate ACE inhibitors due to side effects like cough.[2] Similar eprosartan dosing has been reportedly used in CHF.[46] Again, this is not a specifically approved indication for eprosartan by major regulatory agencies. While certain ARBs (candesartan, valsartan) have specific licensed indications as add-on therapy in CHF under specialist supervision, this does not automatically extend to all drugs in the class.[54]
• COVID-19: One source mentions potential antiviral activity against COVID-19.[20] This remains highly investigational and is not an established therapeutic use.

The distinction between the formally approved indication (hypertension) and these other potential class-associated uses is important. Clinical decisions should primarily be based on approved labeling, recognizing that extrapolation of class effects to individual drugs may not always be appropriate or supported by specific evidence or regulatory approval for that agent.

8. Dosage and Administration

Dosage recommendations for eprosartan are primarily focused on its approved indication for hypertension.

Hypertension (Adults):

• Starting Dose: The usual recommended starting dose for monotherapy in adults who are not volume-depleted is 600 mg taken once daily.[3] European guidelines also recommend 600 mg once daily.[7] Formulations of 400 mg have also been available.[4]
• Maintenance Dose & Titration: The typical maintenance dosage range is 400 mg to 800 mg per day.[3] This total daily dose can be administered either once daily or divided into two doses (twice daily).[3] If the blood pressure response measured at trough (before the next dose) is inadequate with once-daily administration, switching to a twice-daily regimen using the same total daily dose, or increasing the dose, may yield a more satisfactory response.[3] Dose adjustments are generally made at monthly intervals, potentially more aggressively in high-risk patients.[46] It may take 2 to 3 weeks of consistent treatment to observe the maximum blood pressure-lowering effect of a given dose.[3]
• Maximum Dose: Clinical experience with doses exceeding 800 mg per day is limited.[18] Although clinical trials have utilized doses up to 1200 mg daily [40], studies comparing 600 mg versus 1200 mg once daily found no additional benefit with the higher dose.[45] This suggests that 600 mg once daily is often the optimal dose, with potential titration up to 800 mg daily (potentially divided) if necessary.

Combination Therapy (Teveten HCT): When using the fixed-dose combination with hydrochlorothiazide, the usual dose is 600 mg eprosartan / 12.5 mg HCTZ once daily. If blood pressure control is insufficient, the dose may be titrated to 600 mg / 25 mg once daily. This combination product is not intended for initial hypertension therapy.[3]

Special Populations:

• Renal Impairment: No initial dose adjustment is typically needed for mild-to-moderate renal impairment (CrCl ≥30 mL/min).[3] However, due to increased drug exposure in patients with moderate or severe renal impairment (variously defined as CrCl <60 mL/min or <30 mL/min depending on source), the maximum recommended daily dose should not exceed 600 mg.[3] Caution is advised in patients with CrCl <30 mL/min or those undergoing dialysis.[31] The need for dose capping reflects the contribution of renal excretion to overall elimination and the observed pharmacokinetic changes in these patients.[29]
• Hepatic Impairment: For patients with mild-to-moderate hepatic impairment, no initial dose adjustment is generally necessary, but experience is limited, and caution should be exercised.[3] European labeling contraindicates the use of eprosartan in patients with severe hepatic impairment, likely due to the importance of the primary biliary excretion route.[7]
• Geriatric: No initial dose adjustment is required for elderly patients.[3] Eprosartan has been shown to be safe and effective in this age group.[17]
• Pediatric: The safety and efficacy of eprosartan have not been established in children and adolescents. Its use is not recommended in this population.[7]

Administration: Eprosartan tablets are taken orally. Administration can be either once daily or twice daily, and may be taken with or without food.[3] Taking the medication at approximately the same time(s) each day can help with adherence.[49]

9. Safety Profile

Eprosartan is generally well-tolerated, with a safety profile consistent with the ARB class. However, important contraindications, warnings, and potential adverse effects must be considered.

9.1. Contraindications:

Eprosartan should not be used in patients with:

• Known hypersensitivity to eprosartan or any of the tablet excipients.[4]
• Pregnancy, specifically during the second and third trimesters.[7]
• Severe hepatic impairment (according to European labeling).[7]
• Concomitant use of aliskiren (a direct renin inhibitor) in patients with diabetes mellitus.[3] Co-administration should also be avoided in patients with renal impairment (GFR <60 mL/min/1.73 m²).[3]
• Haemodynamically significant bilateral renal artery stenosis or severe stenosis in a solitary functioning kidney (European labeling).[7] Bilateral renal artery stenosis is also listed as a contraindication in some US sources.[46]
• Concomitant use with sparsentan (an endothelin and angiotensin receptor antagonist).[13]

9.2. Warnings and Precautions:

• Fetal Toxicity (US Boxed Warning): This is a critical warning for all drugs acting on the RAAS. Use during the second and third trimesters of pregnancy can cause significant fetal and neonatal harm, including reduced fetal renal function leading to oligohydramnios, fetal lung hypoplasia, skeletal deformations, neonatal skull hypoplasia, anuria, hypotension, reversible or irreversible renal failure, and death.[3] Eprosartan must be discontinued as soon as pregnancy is detected. Women of childbearing potential should be informed of the risks.[4]
• Hypotension: Symptomatic hypotension can occur, particularly at the initiation of therapy or after dose increases, especially in patients who are volume- or salt-depleted (e.g., due to high-dose diuretic therapy, dialysis, vomiting, diarrhea, or dehydration).[3] Volume/salt depletion should be corrected prior to starting eprosartan, or therapy should be initiated under close medical supervision. Dizziness or lightheadedness, especially upon standing, may be symptoms.[32] The risk is increased with dual RAAS blockade.[3]
• Renal Function Impairment: ARBs can cause or worsen renal impairment, particularly in patients whose renal function is dependent on the RAAS, such as those with severe congestive heart failure or renal artery stenosis.[8] Renal function should be monitored periodically, especially in patients with pre-existing kidney disease or those at risk.[3] Concomitant use of NSAIDs or dual RAAS blockade further increases this risk.[3] Dose adjustments are necessary for moderate-to-severe renal impairment (see Section 8).
• Hyperkalemia: Eprosartan can increase serum potassium levels.[46] The risk is higher in patients with renal impairment, heart failure, diabetes, or those taking concomitant medications that also increase potassium levels. These include potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, ACE inhibitors, aliskiren, heparin, trimethoprim, NSAIDs, ciclosporin, and tacrolimus.[3] Serum potassium should be monitored appropriately in at-risk patients.[3]
• Angioedema: Although rare, angioedema (swelling of the face, lips, tongue, throat, extremities) has been reported with ARBs, including eprosartan.[4] If angioedema occurs, eprosartan should be discontinued immediately, and appropriate treatment and monitoring initiated. Intestinal angioedema, presenting with abdominal pain, nausea, and vomiting, has also been reported as a class effect and requires prompt recognition and discontinuation of the drug.[31] Patients with a prior history of angioedema with an ACE inhibitor may have a small increased risk of angioedema with an ARB.[58]
• Valvular Stenosis/Hypertrophic Cardiomyopathy: As with other vasodilators, caution is advised when using eprosartan in patients with hemodynamically significant aortic or mitral valve stenosis, or hypertrophic cardiomyopathy.[31]
• Hepatic Impairment: Use with caution in mild-to-moderate impairment due to limited experience; contraindicated in severe impairment (EMA).[7]
• Primary Hyperaldosteronism: Patients with primary hyperaldosteronism generally do not respond well to drugs inhibiting the RAAS; eprosartan is not recommended.[31]
• Race: Like other RAAS inhibitors, eprosartan may be less effective at lowering blood pressure in Black patients compared to non-Black patients, potentially due to a higher prevalence of low-renin hypertension in this population.[8]
• Lactose Content: Formulations may contain lactose monohydrate, which should be considered in patients with rare hereditary problems of galactose intolerance or lactase deficiency.[8]
• Sprue-like Enteropathy: This is a rare but serious adverse effect associated with some ARBs (most notably olmesartan), characterized by chronic diarrhea, weight loss, and intestinal villous atrophy. While not specifically linked to eprosartan in the provided data, it remains a potential class effect. Symptoms resolve upon drug discontinuation.[2]
• Hepatotoxicity: Eprosartan is associated with a low rate (<2%) of transient serum aminotransferase elevations, similar to placebo rates in clinical trials.[2] These elevations are typically mild and resolve without intervention. While no definitive cases of clinically apparent acute liver injury have been specifically attributed to eprosartan, based on the ARB class effect, it is considered a suspected rare cause (Likelihood Score E*).[2] If liver injury occurs, it typically presents as hepatocellular injury within 1-8 weeks of starting therapy and is generally self-limiting.[2]

9.3. Adverse Effects:

Eprosartan is generally considered well-tolerated.4 Most adverse events reported in clinical trials were mild or moderate in severity, and the overall incidence was similar to that observed with placebo.4 The discontinuation rate due to adverse events was also comparable to placebo (approximately 4% for eprosartan vs. 6.5% for placebo in controlled trials).4

Table 4: Summary of Common Adverse Effects of Eprosartan (>1% incidence in trials)

Adverse Effect	Reported Frequency (%) / Description	Reference(s)
Upper Respiratory Tract Infection	8%	4
Headache	Very Common (EMA); Common (US)	18
Dizziness	Common (EMA); 4.1% (with HCTZ)	3
Cough	4% (Medscape); Less Common (Mayo)	4
Fatigue	2% (Medscape); Common (US label)	4
Rhinitis	Common (US label)	4
Pharyngitis	Common (US label)	4
Abdominal Pain	2% (Medscape); Common (US label)	4
Arthralgia (Joint Pain)	Common (US/EMA labels)	4
Urinary Tract Infection	1%	4
Depression	1%	4
Hypertriglyceridemia	1%	4
Asthenia (Weakness)	Common (EMA label)	31
GI Complaints (Nausea, Diarrhea)	Common (EMA label)	31
Allergic Skin Reactions (Rash, Pruritus)	Common (EMA label)	31

Other adverse events reported at an incidence of 1% or greater in clinical trials (though potentially as or more frequent with placebo) included myalgia, sinusitis, diarrhea, bronchitis, dependent edema, dyspepsia, and chest pain.[4]

Uncommon or rare adverse effects, or those identified post-marketing, include hypotension, hypersensitivity reactions, angioedema (including intestinal angioedema), and impaired renal function (including renal failure in at-risk patients).[31] Rhabdomyolysis is a rare adverse event reported for the ARB class.[4]

When used in the combination product Teveten HCT, adverse effects may be related to either eprosartan or hydrochlorothiazide. HCTZ contributes risks such as electrolyte imbalances (especially hypokalemia) and, rarely, pancreatitis.[18]

9.4. Tolerability Profile:

Compared to ACE inhibitors, eprosartan offers a significant tolerability advantage due to the much lower incidence of cough.9 Its overall tolerability is comparable to placebo 4, and it has demonstrated a good safety profile in elderly patients.40

10. Drug Interactions

Eprosartan has several clinically significant drug interactions, primarily related to potentiation of hypotensive effects, risk of hyperkalemia, and effects on renal function. Its lack of CYP450 metabolism minimizes the risk of metabolic interactions.

• RAAS Inhibitors (ACE Inhibitors, other ARBs, Aliskiren): Co-administration significantly increases the risks of hypotension, hyperkalemia, and deterioration of renal function (including acute renal failure) compared to monotherapy.[3] This "dual blockade" of the RAAS is generally not recommended.[31] Specific contraindications apply to the use of eprosartan with aliskiren in patients with diabetes or significant renal impairment (GFR <60 mL/min).[3] Co-administration with sparsentan is also contraindicated.[13]
• Potassium-Elevating Agents: Concomitant use with potassium-sparing diuretics (e.g., spironolactone, amiloride, triamterene), potassium supplements, salt substitutes containing potassium, or other drugs that can increase serum potassium (e.g., heparin, trimethoprim, ciclosporin, tacrolimus, NSAIDs) increases the risk of hyperkalemia.[3] Careful monitoring of serum potassium is necessary if these combinations are used.[31]
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): This class includes traditional NSAIDs (e.g., ibuprofen, naproxen, ketorolac [60]), selective COX-2 inhibitors (e.g., celecoxib [61], meloxicam [62]), and aspirin.[5] NSAIDs can diminish the antihypertensive effect of eprosartan.[3] More importantly, they can increase the risk of worsening renal function, potentially leading to acute renal failure, especially in patients who are elderly, volume-depleted, or have pre-existing renal compromise.[3] NSAIDs can also contribute to hyperkalemia when used with eprosartan.[5] Renal function should be monitored when NSAIDs are co-administered.[4]
• Lithium: Eprosartan may decrease the renal clearance of lithium, leading to increased serum lithium concentrations and a higher risk of lithium toxicity.[10] Concomitant use should generally be avoided, or lithium levels must be monitored closely.[31]
• Other Antihypertensive Agents: When used with other blood pressure-lowering drugs (including diuretics, beta-blockers, calcium channel blockers, alpha-blockers, etc.), an additive hypotensive effect can be expected.[3] Dose adjustments may be necessary.
• Drugs with Hypotensive Potential: Caution is advised with numerous other drugs that can lower blood pressure, as the combination with eprosartan may lead to excessive hypotension (see examples in outline Section 10).[5]
• Drugs Potentially Reducing Antihypertensive Effect: Some drugs may counteract the effect of eprosartan (see examples in outline Section 10).[5]
• Antidiabetic Agents: ARBs like eprosartan may enhance the hypoglycemic effect of insulin and oral antidiabetic drugs, possibly by improving insulin sensitivity.[46] Blood glucose monitoring may be necessary, especially upon initiation or dose adjustment of eprosartan.
• Drugs with No Significant Interaction: Clinical studies showed no significant pharmacokinetic or pharmacodynamic interactions between eprosartan and digoxin, warfarin, or glyburide.[4] Eprosartan pharmacokinetics were also unaffected by ranitidine, ketoconazole, or fluconazole.[4]
• Synthetic Human Angiotensin II (Giapreza): Eprosartan, being an Ang II receptor blocker, is expected to decrease the pressor response to synthetic Ang II administration.[63]

The most clinically relevant interactions involve the heightened risks of hypotension, hyperkalemia, and renal dysfunction, particularly when eprosartan is combined with other RAAS inhibitors or NSAIDs. Careful patient selection, dose adjustment, and monitoring of blood pressure, serum potassium, and renal function are essential when such combinations are necessary. The lack of significant CYP450-mediated interactions remains a key safety advantage for eprosartan.[3]

11. Regulatory Status and Availability

FDA Approval (United States):

• Eprosartan mesylate (Teveten) received initial FDA approval on December 22, 1997 (NDA 020738), for 300 mg and 400 mg equivalent base strengths.[11] The 600 mg strength was approved on May 27, 1999.[11]
• The fixed-dose combination product, eprosartan mesylate/hydrochlorothiazide (Teveten HCT), was approved on November 1, 2001 (NDA 021268).[29]

EMA Approval (Europe):

• Eprosartan is approved for treating essential hypertension in adults within the European Union.[7] While a specific initial approval date was not found in the provided snippets, its availability is confirmed through Summary of Product Characteristics (SmPC) documents and inclusion in EMA reviews concerning the sartan class (e.g., regarding nitrosamine impurities and RAAS dual blockade).[54] A recent PRAC signal assessment in October 2024 included eprosartan regarding intestinal angioedema.[59]

Discontinuation Status:

• United States: A critical factor regarding eprosartan is its discontinuation in the US market. Both the brand name products, Teveten and Teveten HCT, have been discontinued.[13] Furthermore, the generic single-ingredient eprosartan tablets (manufactured by Mylan) were discontinued in March 2020.[16] The reason cited for these discontinuations was business-related, explicitly stated as not being due to issues with product quality, safety, or efficacy.[15] As a result, eprosartan is currently unavailable for prescription in the United States.[15]
• Other Regions: The availability status outside the US is less clear from the provided data, but the existence of recent European SmPCs and inclusion in ongoing EMA reviews suggests it may remain available in some European countries or other regions.[7]

The complete withdrawal from the US market significantly limits the practical clinical relevance of eprosartan for US-based healthcare providers. Its study remains valuable for comparative pharmacology, understanding historical therapeutic options, and potentially for practitioners in regions where it might still be marketed.

12. Conclusion

Eprosartan is an angiotensin II receptor blocker characterized by a unique non-biphenyl, non-tetrazole structure within the imidazole and thiophene classes. Its primary mechanism involves selective, competitive antagonism of the AT1 receptor, inhibiting the vasoconstrictor and aldosterone-secreting effects of angiotensin II. Evidence also suggests potential secondary mechanisms, including inhibition of sympathetic norepinephrine release and inverse agonism at the AT1 receptor, which may contribute to its overall profile.

Clinically, eprosartan demonstrated efficacy in lowering blood pressure in patients with essential hypertension, comparable to the ACE inhibitor enalapril but with a significantly better tolerability profile, particularly regarding cough incidence. Notable findings from large trials include potential cerebrovascular protective benefits beyond blood pressure lowering (MOSES study) and a possible modest improvement in cognitive function in newly diagnosed hypertensive patients (OSCAR study).

Pharmacokinetically, eprosartan is marked by low oral bioavailability (~13%), high plasma protein binding (~98%), minimal metabolism (not involving the CYP450 system), and predominantly biliary elimination. Discrepancies in reported volume of distribution and elimination half-life likely reflect different measurement contexts (e.g., single vs. multiple dosing, PopPK analysis), with the longer effective duration of action supporting once-daily dosing despite a shorter initial plasma half-life. Dose adjustments are required for moderate-to-severe renal impairment, and it is contraindicated in severe hepatic impairment (EMA).

The safety profile of eprosartan aligns with the ARB class, with the most critical warning concerning fetal toxicity during the second and third trimesters of pregnancy. Monitoring for hypotension (especially in volume-depleted patients), changes in renal function, and hyperkalemia (particularly with interacting drugs like NSAIDs or other RAAS inhibitors) is essential. Generally, it is well-tolerated, representing a valuable alternative for patients intolerant to ACE inhibitors.

Despite its established efficacy and safety profile, eprosartan (both brand and generic formulations) has been discontinued in the United States for commercial reasons. This significantly limits its current therapeutic role in the US, positioning it more as a subject of historical and comparative pharmacological interest for US practitioners. Its clinical utility may persist in other global regions where it remains available. Overall, eprosartan represents a well-studied ARB with some distinct structural and potential mechanistic features, whose practical application is now constrained by market availability in key regions.

Works cited

1. Eprosartan | C23H24N2O4S | CID 5281037 - PubChem, accessed April 30, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Eprosartan
2. Eprosartan - LiverTox - NCBI Bookshelf, accessed April 30, 2025, https://www.ncbi.nlm.nih.gov/books/NBK548507/
3. TEVETEN HCT (eprosartan mesylate/hydrochlorothiazide) 600/12.5mg 600/25mg Rx Only PRESCRIBING INFORMATION WARNING - accessdata.fda.gov, accessed April 30, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021268s019lbl.pdf
4. www.accessdata.fda.gov, accessed April 30, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020738s026lbl.pdf
5. Eprosartan: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed April 30, 2025, https://go.drugbank.com/drugs/DB00876
6. Eprosartan - brand name list from Drugs.com, accessed April 30, 2025, https://www.drugs.com/ingredient/eprosartan.html
7. Eprosartan 300mg film-coated tablets - Summary of Product Characteristics (SmPC) - (emc), accessed April 30, 2025, https://www.medicines.org.uk/emc/product/13584/smpc
8. Summary of Product Characteristics - HPRA, accessed April 30, 2025, https://assets.hpra.ie/products/Human/31646/LicenseSPC_PPA0465-147-001_21112012160122.pdf
9. Full article: The role of eprosartan in the management of essential hypertension: literature review and expert opinion, accessed April 30, 2025, https://www.tandfonline.com/doi/full/10.1080/14779072.2024.2418298?src=
10. EPROSARTAN | 133040-01-4 - ChemicalBook, accessed April 30, 2025, https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0135346.htm
11. Generic Teveten Availability - Drugs.com, accessed April 30, 2025, https://www.drugs.com/availability/generic-teveten.html
12. eprosartan | Ligand page - IUPHAR/BPS Guide to PHARMACOLOGY, accessed April 30, 2025, https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=structure&ligandId=588
13. Teveten Advanced Patient Information - Drugs.com, accessed April 30, 2025, https://www.drugs.com/cons/teveten.html
14. Teveten HCT (eprosartan / hydrochlorothiazide): Uses, Side Effects, Dosage & Reviews, accessed April 30, 2025, https://www.goodrx.com/teveten-hct/what-is
15. Eprosartan: Drug Basics and Frequently Asked Questions - GoodRx, accessed April 30, 2025, https://www.goodrx.com/eprosartan/what-is
16. Eprosartan – Product discontinuation, accessed April 30, 2025, https://professionals.optumrx.com/content/dam/optum3/professional-optumrx/news/rxnews/drug-recalls-shortages/drugwithdrawal_eprosartan_2020-0320.pdf
17. Eprosartan - Wikipedia, accessed April 30, 2025, https://en.wikipedia.org/wiki/Eprosartan
18. Teveten HCT (Eprosartan Mesylate Hydrochlorothiazide Tablets): Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed April 30, 2025, https://www.rxlist.com/teveten-hct-drug.htm
19. eprosartan | Ligand page - IUPHAR/BPS Guide to PHARMACOLOGY, accessed April 30, 2025, https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=588
20. Eprosartan [USAN:INN:BAN] - PubChem, accessed April 30, 2025, https://pubchem.ncbi.nlm.nih.gov/substance/135026481
21. Drug Information | Therapeutic Target Database, accessed April 30, 2025, https://db.idrblab.net/ttd/data/drug/details/D0T7US
22. Eprosartan mesylate | DrugBank Online, accessed April 30, 2025, https://go.drugbank.com/salts/DBSALT000927
23. Compound: EPROSARTAN (CHEMBL813) - ChEMBL - EMBL-EBI, accessed April 30, 2025, https://www.ebi.ac.uk/chembl/explore/compound/CHEMBL813
24. SID 17398013 - PubChem, accessed April 30, 2025, https://pubchem.ncbi.nlm.nih.gov/substance/17398013
25. Eprosartan | C23H24N2O4S - ChemSpider, accessed April 30, 2025, https://www.chemspider.com/Chemical-Structure.4444504.html
26. Eprosartan | RAAS - TargetMol, accessed April 30, 2025, https://www.targetmol.com/compound/eprosartan
27. Eprosartan (SKF-108566J free base) | Angiotensin II Receptor Antagonist, accessed April 30, 2025, https://www.medchemexpress.eu/eprosartan.html
28. Eprosartan | CAS 133040-01-4 | SCBT - Santa Cruz Biotechnology, accessed April 30, 2025, https://www.scbt.com/p/eprosartan-133040-01-4
29. 21-268 TEVETEN Final Print Label - accessdata.fda.gov, accessed April 30, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-268_TEVETEN_prntlbl.pdf
30. Eprosartan: A Review of its Use in the Management of Hypertension - ResearchGate, accessed April 30, 2025, https://www.researchgate.net/publication/7502191_Eprosartan_A_Review_of_its_Use_in_the_Management_of_Hypertension
31. Teveten 600 mg Film-coated Tablets - Summary of Product ..., accessed April 30, 2025, https://www.medicines.org.uk/emc/product/1346/smpc
32. Eprosartan (oral route) - Mayo Clinic, accessed April 30, 2025, https://www.mayoclinic.org/drugs-supplements/eprosartan-oral-route/description/drg-20063692
33. Full article: The role of eprosartan in the management of essential hypertension: literature review and expert opinion, accessed April 30, 2025, https://www.tandfonline.com/doi/full/10.1080/14779072.2024.2418298?src=exp-la
34. TEVETEN® (eprosartan mesylate) 400mg 600mg - accessdata.fda.gov, accessed April 30, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020738s027lbl.pdf
35. Eprosartan for the treatment of hypertension - PubMed, accessed April 30, 2025, https://pubmed.ncbi.nlm.nih.gov/12517247/
36. Evaluation of the 24-hour blood pressure effects of eprosartan in patients with systemic hypertension - Oxford Academic, accessed April 30, 2025, https://academic.oup.com/ajh/article/14/12/1248/153847
37. Eprosartan: a review of its use in hypertension - PubMed, accessed April 30, 2025, https://pubmed.ncbi.nlm.nih.gov/19911859/
38. Eprosartan - PubMed, accessed April 30, 2025, https://pubmed.ncbi.nlm.nih.gov/9585867/
39. Proteinuria Medication: ACE Inhibitors, Angiotensin II Receptor Antagonists (ARBs), Diuretics, Loop, Diuretics, Thiazide, Aldosterone Antagonists, Selective, Calcium Channel Antagonists, Sodium-Glucose Cotransporter-2 (SGL2) Inhibitor , Glucagon-like Peptide 1 Receptor (GLP-1) Receptor Agonists, Mineralocorticoid Antagonist - Medscape Reference, accessed April 30, 2025, https://emedicine.medscape.com/article/238158-medication
40. Pharmacokinetics of eprosartan in healthy subjects, patients with hypertension, and special populations - PubMed, accessed April 30, 2025, https://pubmed.ncbi.nlm.nih.gov/10213525/
41. Angiotensin II-Receptor Antagonists: An Overview - Page 8 - Medscape, accessed April 30, 2025, https://www.medscape.com/viewarticle/406895_8
42. Effect of age and gender on the pharmacokinetics of eprosartan - PMC, accessed April 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC1873684/
43. TEVETEN® HCT (eprosartan mesylate/hydrochlorothiazide)600/12.5mg 600/25mg - accessdata.fda.gov, accessed April 30, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021268s015s016lbl.pdf
44. Eprosartan A Review of its Use in Hypertension - ResearchGate, accessed April 30, 2025, https://www.researchgate.net/publication/297523498_Eprosartan_A_Review_of_its_Use_in_Hypertension
45. Evaluation of the 24-hour blood pressure effects of eprosartan in ..., accessed April 30, 2025, https://pubmed.ncbi.nlm.nih.gov/11775134/
46. Teveten (eprosartan) dosing, indications, interactions, adverse effects, and more, accessed April 30, 2025, https://reference.medscape.com/drug/teveten-eprosartan-342318
47. Eprosartan Niche 300 mg Film-coated Tablets - Summary of Product Characteristics, accessed April 30, 2025, https://assets.hpra.ie/products/Human/24341/LicenseSPC_PA1063-052-001_29052015154051.pdf
48. Eprosartan and hydrochlorothiazide (oral route) - Mayo Clinic, accessed April 30, 2025, https://www.mayoclinic.org/drugs-supplements/eprosartan-and-hydrochlorothiazide-oral-route/description/drg-20074921
49. Eprosartan | Saint Luke's Health System, accessed April 30, 2025, https://www.saintlukeskc.org/health-library/eprosartan
50. The efficacy and tolerance of one or two daily doses of eprosartan in ..., accessed April 30, 2025, https://pubmed.ncbi.nlm.nih.gov/10100104/
51. Eprosartan | C23H24N2O4S | CID 5281037 - PubChem, accessed April 30, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/DTXSID0022989
52. Hypertensive Completed Phase Trials for Eprosartan (DB00876) | DrugBank Online, accessed April 30, 2025, https://go.drugbank.com/indications/DBCOND0046062/clinical_trials/DB00876?status=completed
53. Teveten HCT, Teveten Plus (eprosartan-hydrochlorothiazide) dosing, indications, interactions, adverse effects, and more - Medscape, accessed April 30, 2025, https://reference.medscape.com/drug/teveten-hct-teveten-plus-eprosartan-hydrochlorothiazide-342346
54. Renin-angiotensin-system (RAS)-acting agents - referral | European Medicines Agency (EMA), accessed April 30, 2025, https://www.ema.europa.eu/en/medicines/human/referrals/renin-angiotensin-system-ras-acting-agents
55. Eprosartan Completed Phase 4 Trials for Healthy Volunteers (HV) | DrugBank Online, accessed April 30, 2025, https://go.drugbank.com/drugs/DB00876/clinical_trials?conditions=DBCOND0114743&phase=4&status=completed
56. Eprosartan Completed Phase 3 Trials for Essential Hypertension Treatment - DrugBank, accessed April 30, 2025, https://go.drugbank.com/drugs/DB00876/clinical_trials?conditions=DBCOND0029603&phase=3&purpose=treatment&status=completed
57. Eprosartan Completed Phase 4 Trials for Essential Hypertension | DrugBank Online, accessed April 30, 2025, https://go.drugbank.com/drugs/DB00876/clinical_trials?conditions=DBCOND0029603&phase=4&status=completed
58. Angiotensin II receptor blocker - Wikipedia, accessed April 30, 2025, https://en.wikipedia.org/wiki/Angiotensin_II_receptor_blocker
59. PRAC recommendations on signals adopted at the 28-31 October 2024 PRAC_en - EMA, accessed April 30, 2025, https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendations-signals-adopted-28-31-october-2024-prac-meeting_en.pdf
60. Ketorolac (oral route, injection route) - Mayo Clinic, accessed April 30, 2025, https://www.mayoclinic.org/drugs-supplements/ketorolac-oral-route-injection-route/description/drg-20066882
61. Celecoxib (oral route) - Mayo Clinic, accessed April 30, 2025, https://www.mayoclinic.org/drugs-supplements/celecoxib-oral-route/description/drg-20068925
62. Meloxicam (oral route) - Mayo Clinic, accessed April 30, 2025, https://www.mayoclinic.org/drugs-supplements/meloxicam-oral-route/description/drg-20066928
63. Giapreza (synthetic human angiotensin II) dosing, indications, interactions, adverse effects, and more - Medscape, accessed April 30, 2025, https://reference.medscape.com/drug/giapreza-synthetic-human-angiotensin-ii-1000206
64. Drug Approval Package: Tevetan NDA 20738 - accessdata.fda.gov, accessed April 30, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020738_tevetan_toc.cfm
65. www.accessdata.fda.gov, accessed April 30, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-268_Teveten.cfm#:~:text=Approval%20Date%3A%2011%2F01%2F2001
66. Angiotensin-II-receptor antagonists (sartans) containing a tetrazole group - referral - EMA, accessed April 30, 2025, https://www.ema.europa.eu/en/medicines/human/referrals/angiotensin-ii-receptor-antagonists-sartans-containing-tetrazole-group