Aliskireno
Aliskireno Uses, Dosage, Side Effects, Food Interaction and all others data.
Aliskireno is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Ang II also functions within the Renin-Angiotensin-Aldosterone System (RAAS) as a negative inhibitory feedback mediator within the renal parenchyma to suppress the further release of renin. Thus, reductions in Ang II levels suppress this feedback loop, leading to further increased plasma renin concentrations (PRC) and subsequent activity (PRA). This disinhibition effect can be potentially problematic for ACE inhibitor and ARB therapy, as increased PRA could partially overcome the pharmacologic inhibition of the RAAS. As aliskiren is a direct inhibitor of renin activity, blunting of PRA despite the increased PRC (from loss of the negative feedback) may be clinically advantageous. The effect of aliskiren on bradykinin levels is unknown.
Aliskireno reduces blood pressure by inhibiting renin. This leads to a cascade of events that decreases blood pressure, lowering the risk of fatal and nonfatal cardiovascular events including stroke and myocardial infarction.
| Trade Name | Aliskireno |
| Availability | Prescription only |
| Generic | Aliskiren |
| Aliskiren Other Names | Aliskiren, Aliskireno |
| Related Drugs | amlodipine, lisinopril, metoprolol, losartan, furosemide, hydrochlorothiazide |
| Type | |
| Formula | C30H53N3O6 |
| Weight | Average: 551.7583 Monoisotopic: 551.393436443 |
| Protein binding | The plasma protein binding of aliskiren ranges from 47-51%. |
| Groups | Approved, Investigational |
| Therapeutic Class | Direct Renin Inhibitors |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Treating high blood pressure. It may be used alone or with other medicines. Aliskireno is a direct renin inhibitor. It works by relaxing blood vessels, which lowers blood pressure and helps the heart to pump blood more easily.
Aliskireno is also used to associated treatment for these conditions: High Blood Pressure (Hypertension)
How Aliskireno works
Aliskireno 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.
Aliskireno 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
Aliskireno 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. 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. 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.
MONITOR: High-fat meals can substantially reduce the gastrointestinal absorption of aliskiren.
MANAGEMENT: To ensure steady systemic drug levels and therapeutic effects, patients should establish a routine pattern for administration of aliskiren with regard to meals.
Aliskireno 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
Aliskireno Disease Interaction
Volume of Distribution
Unchanged aliskiren accounts for about 80% of the drug found in the plasma.
Elimination Route
Aliskireno 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
Aliskireno 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
Aliskireno 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 Aliskireno
Aliskireno contains Aliskiren see full prescribing information from innovator Aliskireno Monograph, Aliskireno MSDS, Aliskireno FDA label
FAQ
What is Aliskireno?
Aliskireno is a medication that belongs to a class of drugs known as renin inhibitors. It is used to treat high blood pressure (hypertension) and is typically prescribed when other blood pressure medications have not been effective.
How does Aliskireno work?
Aliskireno works by blocking the activity of the renin-angiotensin-aldosterone system (RAAS), which is a hormone system that regulates blood pressure. By inhibiting the action of renin, an enzyme that starts the RAAS cascade, Aliskireno helps to lower blood pressure.
How is Aliskireno taken?
Aliskireno is taken orally in tablet form. The medication is usually taken once daily at the same time each day, with or without food.
What are the side effects of Aliskireno?
Some common side effects of Aliskireno may include diarrhea, headache, dizziness, cough, and fatigue. Less common but more serious side effects may include allergic reactions, kidney problems, and low blood pressure.
Who should not take Aliskireno?
Aliskireno should not be taken by pregnant women or individuals with a history of angioedema (swelling of the face, lips, tongue, or throat). It may also not be suitable for individuals with kidney disease, liver disease, or diabetes.
What medications may interact with Aliskireno?
Aliskireno may interact with other blood pressure medications, diuretics, and certain drugs that affect the RAAS system. Patients should inform their healthcare provider of all medications they are taking before starting treatment with Aliskireno.
Can Aliskireno be taken during pregnancy or breastfeeding?
Aliskireno is not recommended for use during pregnancy or breastfeeding as it may harm the fetus or infant.
How long does it take for Aliskireno to start working?
The time it takes for Aliskireno to start working may vary depending on the individual and the severity of their high blood pressure. Patients should continue taking the medication as prescribed and may need regular blood pressure monitoring to ensure that the medication is effective.
Can Aliskireno be stopped suddenly?
Patients should not stop taking Aliskireno suddenly without first consulting their healthcare provider. Stopping the medication abruptly may cause a sudden increase in blood pressure.
What should I do if I miss a dose of Aliskireno?
If a dose of Aliskireno is missed, patients should take the missed dose as soon as they remember. If it is close to the time for the next dose, patients should skip the missed dose and resume their regular dosing schedule.
How should Aliskireno be stored?
Aliskireno should be stored at room temperature, away from heat, light, and moisture. The medication should be kept out of reach of children and should be properly disposed of after use.
Is Aliskireno addictive?
No, Aliskireno is not addictive. It is not classified as a controlled substance and does not produce a high or any psychoactive effects.
Can Aliskireno be used to treat other conditions besides high blood pressure?
At present, Aliskireno is only approved for the treatment of high blood pressure. However, it is being investigated for its potential use in other conditions, such as heart failure and diabetic nephropathy.
Can Aliskireno cause low blood pressure (hypotension)?
Yes, Aliskireno can cause low blood pressure in some patients. This may be more likely to occur in individuals who are dehydrated, have kidney problems, or are taking other blood pressure medications.
Can Aliskireno be taken with food?
Aliskireno can be taken with or without food. However, taking the medication with a high-fat meal may decrease its absorption and effectiveness.
How often should blood pressure be monitored while taking Aliskireno?
Patients taking Aliskireno should have their blood pressure monitored regularly, especially during the first few weeks of treatment. The frequency of blood pressure monitoring may vary depending on the individual and their response to the medication.
Can Aliskireno be taken with other medications for high blood pressure?
Aliskireno may be taken with other medications for high blood pressure, such as diuretics or calcium channel blockers. However, the dose of these medications may need to be adjusted, and patients should always consult their healthcare provider before starting or changing any medications.
How long is Aliskireno typically prescribed for?
The duration of Aliskireno treatment may vary depending on the individual and their response to the medication. Patients may need to take the medication for an extended period of time or even indefinitely to maintain their blood pressure control.
Can Aliskireno cause kidney problems?
Aliskireno has been associated with an increased risk of kidney problems, particularly in patients with pre-existing kidney disease or diabetes. Patients should inform their healthcare provider of any changes in their kidney function while taking Aliskireno.
How does Aliskireno compare to other blood pressure medications?
Aliskireno is a relatively new medication for high blood pressure and has not been studied extensively in comparison to other blood pressure medications. However, it may be particularly effective in patients with high renin levels and has a lower incidence of side effects compared to some other medications.
