Easrin

Uses

Treating high blood pressure. It may be used alone or with other medicines. Easrin is a direct renin inhibitor. It works by relaxing blood vessels, which lowers blood pressure and helps the heart to pump blood more easily.

Easrin is also used to associated treatment for these conditions: High Blood Pressure (Hypertension)

How Easrin works

Easrin is a renin inhibitor. Renin is secreted by the kidneys when blood volume and renal perfusion decrease. It normally cleaves the protein angiotensinogen to form angiotensin I. Angiotensin I is then converted to angiotensin II, an active protein. Angiotensin II is a potent vasoconstrictor that causes the release of catecholamines into the circulation. It also promotes the secretion of aldosterone in addition to sodium reabsorption, increasing blood pressure. Additionally, angiotensin II acts on the adrenal cortex where it stimulates aldosterone release. Aldosterone increases sodium reabsorption and potassium excretion in the nephron.

Easrin prevents the above process via binding to renin at its active site, stopping the cleavage of angiotensin, in turn inhibiting the formation of angiotensin I. This ends the cascade of angiotensin II mediated mechanisms that normally increase blood pressure.

Dosage

Easrin dosage

Initial adult dose: 150 mg orally once a day.

Maintenance adult dose: The dosage may be increased to 300 mg daily if blood pressure is not adequately controlled. No dosage adjustment is recommended based on gender, age, body weight or race.

Safety and efficacy have not been established in patients younger than 18 years. AUC is increased in elderly patients 65 years of age and older.

Side Effects

Skin rash (1%), Diarrhea (2%), Increased creatine phosphokinase, Increased blood urea nitrogen (≤7%), increased serum creatinine (≤7%), RespirCough (1%)

Limited to important or life-threatening: Anaphylaxis, decreased hematocrit, decreased hemoglobin, gastroesophageal reflux disease, hepatic insufficiency, hyperkalemia, increased uric acid, nausea, rhabdomyolysis, seizure, severe hypotension, Stevens-Johnson syndrome, tonic-clonic seizures, vomiting

Toxicity

The oral LD50 of aliskiren in rats is >2000 mg/kg. Overdose information is limited in the literature, however, an overdose with aliskiren is likely to result in hypotension. Supportive treatment should be initiated in the case of an overdose.

Interaction

Major: Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.

Moderate: Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.

Minor: Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.

Food Interaction

• Do not take with or immediately after a high-fat meal. The absorption of aliskiren is substantially reduced by taking it with high-fat meals.
• Take with or without food. Take consistently at the same time in regard to meals.

[Moderate] GENERALLY AVOID: Coadministration with orange, apple, or grapefruit juice may significantly decrease the oral bioavailability and renin-inhibiting effect of aliskiren.

The exact mechanism of interaction is unknown, but may include inhibition of OATP2B1-mediated influx of aliskiren in the small intestine, formation of insoluble complexes between fruit juice constituents and aliskiren, and

In 12 healthy volunteers, 200 mL of either orange juice or apple juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 80% and 60%, respectively, compared to water.

Plasma renin activity was 87% and 67% higher at 24 hours postdose when aliskiren was administered with orange juice and apple juice, respectively, compared to water.

No significant differences were observed in the blood pressure or heart rate between treatments.

However, this may be due to the delayed onset of aliskiren's blood pressure-lowering effect, which would not be apparent following a single dose.

A similar pharmacokinetic interaction has been reported with grapefruit juice.

In 11 healthy volunteers, 200 mL of normal strength grapefruit juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren Cmax and AUC by 81% and 61%, respectively, but there was no change in plasma renin activity compared to water.

A high degree of interpatient variability was observed with all three interactions.

MONITOR: High-fat meals can substantially reduce the gastrointestinal absorption of aliskiren.

According to the product labeling, administration of aliskiren with a high-fat meal decreased the mean peak plasma concentration (Cmax) and systemic exposure (AUC) by 85% and 71%, respectively.

In clinical trials, however, aliskiren was administered without a fixed requirement in relation to meals.

MANAGEMENT: To ensure steady systemic drug levels and therapeutic effects, patients should establish a routine pattern for administration of aliskiren with regard to meals.

Coadministration with orange, apple, or grapefruit juice should be avoided, especially if these juices are to be consumed on a regular basis or shortly before or after aliskiren dosing.

Easrin Drug Interaction

Moderate: aspirin, aspirin, celecoxib, celecoxib, atorvastatin, atorvastatinUnknown: fluticasone / salmeterol, fluticasone / salmeterol, nebivolol, nebivolol, rosuvastatin, rosuvastatin, insulin glargine, insulin glargine, amlodipine, amlodipine, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Easrin Disease Interaction

Major: diabetesModerate: hypotension, renal impairment

Volume of Distribution

Unchanged aliskiren accounts for about 80% of the drug found in the plasma.

Elimination Route

Easrin is absorbed in the gastrointestinal tract and is poorly absorbed with a bioavailability between 2.0 and 2.5%. Peak plasma concentrations of aliskiren are achieved between 1 to 3 hours after administration. Steady-state concentrations of aliskiren are achieved within 7-8 days of regular administration.

Half Life

Plasma half-life for aliskiren can range from 30 to 40 hours with an accumulation half-life of about 24 hours.

Clearance

Easrin is partially cleared in the kidneys, and safety data have not been established for patients with a creatinine clearance of less than 30 mL/min. One pharmacokinetic study revealed an average renal clearance of 1280 +/- 500 mL/hour in healthy volunteers.

Elimination Route

Easrin is mainly excreted via the hepatobiliary route and by oxidative metabolism by hepatic cytochrome enzymes. Approximately one-quarter of the absorbed dose appears in the urine as unchanged parent drug. One pharmacokinetic study of radiolabeled aliskiren detected 0.6% radioactivity in the urine and more than 80% in the feces, suggesting that aliskiren is mainly eliminated by the fecal route.

Pregnancy & Breastfeeding use

If pregnancy is detected, discontinue aliskiren as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Contraindication

Hypersensitivity to aliskiren or any component of the formulation; concomitant use with an ACE inhibitor or ARB in patients with diabetes mellitus History of angioedema with aliskiren, ACE inhibitors, or ARBs; hereditary or idiopathic angioedema; pregnancy, breast-feeding; concomitant use with ACE inhibitors or ARBs in patients with GFR <60 mL/minute/1.73 m2; patients <2 years of age.

Special Warning

Renal Dose Adjustments:

• Mild to moderate renal dysfunction (CrCl 30 mL/min or greater): No adjustment recommended.
• Severe renal dysfunction (CrCl 30 mL/min or less): Not recommended

Liver Dose Adjustments

: No adjustment recommended

Storage Condition

Store aliskiren at room temperature, between 15° to 30° C. Store in the original bottle, away from heat, moisture, and light. Keep aliskiren out of the reach of children and away from pets.

Innovators Monograph

You find simplified version here Easrin