Riprazo HCT

Uses

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

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

How Riprazo HCT works

Aliskiren 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.

Aliskiren 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

Riprazo HCT 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.

Volume of Distribution

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

Elimination Route

Aliskiren 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

Aliskiren 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

Aliskiren 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

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