Erastapex Uses

• Erastapex indications
• Erastapex description
• Erastapex dosage
• Erastapex interactions
• Erastapex side effects
• Erastapex contraindications

Erastapex indications

Erastapex is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with Erastapex.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

It may be used alone or in combination with other antihypertensive agents.

Erastapex description

Erastapex 10 mg Tablet: Each tablet contains 10 mg of Erastapex.

Erastapex 20 mg Tablet: Each tablet contains 20 mg of Erastapex.

Erastapex 40 mg Tablet: Each tablet contains 40 mg of Erastapex.

Erastapex (Erastapex), a prodrug, which is hydrolysed to the active metabolite Erastapex during absorption from the gastrointestinal tract. Erastapex is a selective AT₁ subtype angiotensin II receptor antagonist.

Erastapex is described chemically as (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylate. Alternatively, it can be described as 2,3-dihydroxy-2-butenyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonate.

Its empirical formula is C₂₉H₃₀N₆O₆.

Erastapex is a white to light yellowish-white powder or crystalline powder with a molecular weight of 558.59. It is practically insoluble in water and sparingly soluble in methanol.

Erastapex dosage

Adults: Dosage must be individualized. The usual recommended starting dose of Erastapex is 20 mg once daily when used as monotherapy in patients who are not volume-contracted. If additional blood pressure reduction is required, Erastapex dose may be increased to a maximum of 40 mg daily or hydrochlorothiazide therapy may be added.

The antihypertensive effect of Erastapex is substantially present within 2 weeks of initiating therapy and is maximal by about 8 weeks after initiating therapy. This should be borne in mind when considering changing the dose regimen for any patient.

Elderly: No adjustment of dosage is generally required in the elderly. If up-titration to the maximum dose of 40 mg daily is required, blood pressure should be closely monitored.

Renal Impairment: Dosage of Erastapex should be individualized in patients with renal impairment.

The maximum dose in patients with mild to moderate renal impairment (creatinine clearance of 20–60 mL/min) is 20 mg Erastapex once daily, owing to limited experience of higher dosages in this patient group. The use of Erastapex in patients with severe renal impairment (creatinine clearance <20 mL/min) is not recommended, since there is only limited experience in this patient group.

There is no experience in the use of Erastapex in patients requiring dialysis.

Hepatic Impairment: No adjustment of dosage recommendations is required for patients with mild hepatic impairment. In patients with moderate hepatic impairment, an initial dose of 10 mg Erastapex once daily is recommended and the maximum dose should not exceed 20 mg once daily. Close monitoring of blood pressure and renal function is advised in hepatically-impaired patients who are already receiving diuretics and/or other antihypertensive agents. There is no experience of Erastapex in patients with severe hepatic impairment, therefore use is not recommended in this patient group. Erastapex should not be used in patients with biliary obstruction.

Children: The safety and efficacy of Erastapex in children and adolescents below 18 years has not been established. No data are available.

Administration: In order to assist compliance, it is recommended that Erastapex tablets be taken at about the same time each day, with or without food, for example at breakfast time.

The tablet should be swallowed with a sufficient amount of fluid (e.g. one glass of water). The tablet should not be chewed.

Erastapex interactions

Erastapex

No significant drug interactions were reported in studies in which Erastapex was co-administered with hydrochlorothiazide, digoxin or warfarin in healthy volunteers. The bioavailability of Erastapex was not significantly altered by the co-administration of antacids [Al(OH)3/Mg(OH)2]. Erastapex is not metabolized by the cytochrome P450 system and has no effects on P450 enzymes; thus, interactions with drugs that inhibit, induce or are metabolized by those enzymes are not expected.

Hydrochlorothiazide

When administered concurrently the following drugs may interact with thiazide diuretics:

Alcohol, Barbiturates, Or Narcotics– potentiation of orthostatic hypotension may occur.

Antidiabetic Drugs (oral agents and insulin)– dosage adjustment of the antidiabetic drug may be required.

Other Antihypertensive Drugs– additive effect or potentiation.

Cholestyramine and Colestipol Resins– absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.

Corticosteroids, ACTH– intensified electrolyte depletion, particularly hypokalemia.

Pressor Amines (e.g. Norepinephrine)– possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal Muscle Relaxants, Non depolarizing (e.g. Tubocurarine)– possible increased responsiveness to the muscle relaxant.

Lithium– should not generally be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparation with Erastapex-hydrochlorothiazide.

Non-steroidal Anti-inflammatory Drugs– in some patients the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when Erastapex-hydrochlorothiazide tablets and non-steroidal anti-inflammatory agents are used concomitantly, the patients should be observed closely to determine if the desired effect of the diuretic is obtained

Erastapex side effects

Erastapex has been evaluated for safety in >3,825 patients/subjects, including >3,275 patients treated for hypertension in controlled trials. This experience included about 900 patients treated for at least 6 months and >525 for at least 1 year. Treatment with Erastapex was well tolerated, with an incidence of adverse events similar to placebo. Events generally were mild, transient and had no relationship to the dose of Erastapex.

The overall frequency of adverse events was not dose-related. Analysis of gender, age and race groups demonstrated no differences between Erastapex- and placebo-treated patients. The rate of withdrawals due to adverse events in all trials of hypertensive patients was 2.4% (ie, 79/3,278) of patients treated with Erastapex and 2.7% (ie, 32/1,179) of control patients. In placebo-controlled trials, the only adverse event that occurred in >1% of patients treated with Erastapex and at a higher incidence versus placebo was dizziness (3% vs 1%).

The following adverse events occurred in placebo-controlled clinical trials at an incidence of >1% of patients treated with Erastapex, but also occurred at about the same or greater incidence in patients receiving placebo: Back pain, bronchitis, increased creatine phosphokinase, diarrhea, headache, hematuria, hyperglycemia, hypertriglyceridemia, influenza-like symptoms, pharyngitis, rhinitis and sinusitis.

The incidence of cough was similar in placebo (0.7%) and Erastapex (0.9%) patients. Other (potentially important) adverse events that have been reported with an incidence of >0.5%, whether or not attributed to treatment, in the >3,100 hypertensive patients treated with Erastapex monotherapy in controlled or open-label trials are listed as follows: Body as a Whole: Chest pain, peripheral edema.

Central and Peripheral Nervous System: Vertigo.

Gastrointestinal: Abdominal pain, dyspepsia, gastroenteritis, nausea.

Heart Rate and Rhythm Disorders: Tachycardia.

Metabolic and Nutritional Disorders: Hypercholesterolemia, hyperlipemia, hyperuricemia.

Musculoskeletal: Arthralgia, arthritis, myalgia.

Skin and Appendages: Rash.

Facial edema was reported in 5 patients receiving Erastapex. Angioedema has been reported with other angiotensin II antagonists.

Laboratory Test Findings: In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of Erastapex.

Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g/dL and 0.3 volume percent, respectively) were observed.

Liver Function Tests: Elevations of liver enzymes and/or serum bilirubin were observed infrequently. Five patients (0.1%) assigned to Erastapex and 1 patient (0.2%) assigned to placebo in clinical trials were withdrawn because of abnormal liver chemistries (transaminases or total bilirubin). Of the 5 Erastapex patients, 3 had elevated transaminases, which were attributed to alcohol use, and 1 had a single elevated bilirubin value, which normalized while treatment continued.

Clinical Trial Experience: Dizziness has been reported commonly (≥1%, <10% incidence) in clinical trials with Erastapex.

Post-Launch Experience: In post-launch experience, adverse drug reactions which have been reported very rarely (<0.01% incidence) are: Peripheral edema, headache, cough, abdominal pain, nausea, vomiting, diarrhea, sprue-like enteropathy anaphylactic reaction, rash, pruritus, angioedema, acute renal failure, increased hepatic enzymes and blood creatinine, hyperkalaemia, myalgia and asthenic conditions eg, asthenia, fatigue, lethargy, malaise. Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.

Erastapex contraindications

Hypersensitivity to Erastapex or to any of the excipients of Erastapex.

Biliary obstruction.

Do not co-administer aliskiren with Erastapex in patients with diabetes.

Use in pregnancy: There is no experience with the use of Erastapex in pregnant women. However, drugs that act directly on the renin-angiotensin system administered during the 2nd and 3rd trimesters of pregnancy have been reported to cause foetal and neonatal injury (hypotension, renal dysfunction, oliguria and/or anuria, oligohydramnios, skull hypoplasia, intrauterine growth retardation, lung hypoplasia, facial abnormalities, limb contracture) and even death.

Thus, as for any drug in this class, Erastapex is contraindicated during the 2nd and 3rd trimesters of pregnancy. In addition, Erastapex must not be used during the 1st trimester. If pregnancy occurs during therapy, Erastapex must be discontinued as soon as possible.

Use in lactation: Erastapex is excreted in the milk of lactating rats, but it is not known whether Erastapex is excreted in human milk. Mothers must not breastfeed if they are taking Erastapex.

Active ingredient matches for Erastapex:

Olmesartan Medoxomil in Egypt.

Olmesartan

References

1. PubChem. "Olmesartan". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
2. DrugBank. "Olmesartan". http://www.drugbank.ca/drugs/DB00275 (accessed September 17, 2018).
3. DTP/NCI. "Olmesartan: The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents.". https://dtp.cancer.gov/dtpstandard/s... (accessed September 17, 2018).

Reviews

User reports

Consumer reviews

Information checked by Dr. Sachin Kumar, MD Pharmacology