Aliskiren - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview

Aliskiren is an authorized medicine that is used to bring down elevated blood pressure (hypertension). It comes under the category of direct renin inhibitors. Treatment of hypertension using Aliskiren is endorsed and accepted by the drug regulatory body of the United States - the Food and Drug Administration (FDA). It is equally effective for children (more than 6 years) and adults. Apart from hypertension, Aliskiren is also used to decrease the likelihood of certain cardiovascular disorders. At times, it is prescribed along with other blood pressure-lowering agents. It is available only in the form of pills.

How Does an Aliskiren Work?

Aliskiren brings down elevated blood pressure by specifically inhibiting and blocking the enzyme renin. Certain unique and functional groups of cells in the kidney called juxtaglomerular cells are the chief production unit of renin. Renin has dual functions, it performs the role of an enzyme as well as a hormone, and it potentially activates the chemical that initiates the constriction of blood vessels. Blood pressure rises with the contraction and tightening of the blood vessels. The entire sequence of processes involved in blood pressure elevation can be controlled by blocking the renin. In this way, Aliskiren works for patients suffering from hypertension.

Uses:

Aliskiren is essentially advised for tackling the raised blood pressure. Certain studies revealed that Aliskiren potentially lowers the possibility of serious events like strokes.

Available Doses and Dosage Forms:

Aliskiren is preferably advised for oral intake in the form of pills and pellets. Combination pills containing other antihypertensive drugs along with Aliskiren are also available and often prescribed for appropriate patients. Patients are advised to take only one tablet per day. Aliskiren-only tablets are specifically available in two distinct doses, 150 milligrams (mg) and 300 mg. While 37.5 mg is the dose available in the pellet form of Aliskiren. It is also marketed in combination with Hydrochlorothiazide and Amlodipine of varying concentrations.

• Aliskiren-Only Tablets: 150 mg and 300 mg.

• Aliskiren Pellets: 37.5 mg.

• Aliskiren With Hydrochlorothiazide: 150-12.5 mg, 150-25 mg, 300-12.5 mg, 300-25 mg.

• Aliskiren With Amlodipine and Hydrochlorothiazide: 150-5-12.5 mg, 300-5-25 mg, 300-5-12.5 mg, 300-10-25 mg, 300-10-12.5 mg.

Warnings:

• Concurrent Use: Aliskiren should not be taken in the presence of significant renal damage, along with other medicines like angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) in diabetic patients.

• Fetal Toxicity: Pregnant women are not supposed to take Aliskiren-containing tablets. Aliskiren has the potential to negatively impact the growing child in the womb and could even result in skeletal, and functional deformities and death. If tested positive for pregnancy, withdraw the medicine as early as possible.

• Renal Damage: Aliskiren may significantly enhance renal damage and impairment. It potentially elevates the likelihood of developing renal failure.

• Angioedema: Certain patients reported extensive swelling involving the head, face, and neck following Aliskiren intake. When the swelling extends into the tongue, larynx, and associated airway tract, it blocks and interferes with breathing which can be potentially life-threatening and therefore requires instantaneous medical attention.

• Fainting: Loss of consciousness is often encountered with Aliskiren therapy due to a remarkable collapse in blood pressure, as a result of the drug action.

For Patients:

What Is Hypertension?

Hypertension is a medical condition in which the patient exhibits a consistent and remarkable rise in blood pressure. There is a certain pressure or force with which the blood flows inside the blood vessels. As a result, the flowing blood pushes the wall of the blood vessel, which is manifested in the form of blood pressure. There is a normal range for blood pressure that is considered perfectly normal for an individual, 120/80 millimeters of mercury (mm of Hg) is depicted as the normal range. Any value within this span falls under the normal blood pressure category. A deviation from this span signifies either a rise or fall in blood pressure. However, the normal range exhibits slight variations on an individual basis based on age and other related factors. Hypertension demands medical attention; otherwise, it potentially brings about several medical complications like stroke, heart failure, and cardiac arrest.

When and Why Is Aliskiren Prescribed?

Aliskiren is extensively advised for controlling persistent and remarkable hikes in blood pressure. It aids in bringing the blood pressure back to its normal range. However, it is not curative in nature, it can tackle hypertension as long as it is administered. Aliskiren-containing antihypertensive medicines work well for primary hypertension. When the raised blood pressure is independent of other underlying conditions, it is medically known as primary hypertension. If hypertension persists over a longer period, it may precipitate complications that could endanger an individual’s life.

Things to Inform the Doctor Before Taking Aliskiren:

There are certain things that the patient should inform the physician before starting with Aliskiren-containing medicines for hypertension. Some of the relevant information that should be shared with the concerned doctor includes the following:

• Any previous history of allergic response towards Aliskiren-containing medicines should be informed before starting with the medicines. In such cases, further administration of Aliskiren may initiate a severe and potentially dangerous allergic reaction (anaphylaxis).

• If the patient is currently planning for pregnancy in the near future, keep the doctor updated regarding that. Aliskiren is not safe during pregnancy, it can have serious implications on the child in the womb.

• Lactating women (breastfeeding) should notify the doctor because there is no conclusive evidence suggesting that Aliskiren is safe during breastfeeding. However, certain animal studies figured out that it is unsafe.

• The patient should give all the pieces of information regarding the currently undertaking medications, especially angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. It helps to avoid possible drug interactions and their impacts on the patient’s health.

• If the patient suffers from other underlying systemic diseases like diabetes (raised sugar level in blood), renal diseases, and many more, it must be disclosed to the doctor before taking Aliskiren.

Things to Consider While Taking Aliskiren:

While on Aliskiren therapy, certain factors demand immediate attention. Some of them include the following:

• Any form of side effect or adverse reaction that develops while on Aliskiren should be reported and discussed with the doctor immediately so that the doctor could either alter the dosage or may change the medicine if required.

• If the patient became pregnant while on Aliskiren treatment, the patient should withdraw the medicine and notify the doctor at the earliest.

• If the patient experiences frequent fainting and collapse while on the treatment, it should be reported to the doctor without fail as it might be an indication of hypotension (diminished blood pressure).

What Are the Instructions to Be Followed While on Aliskiren?

• Patients are advised to strictly stick to the dosage schedule prescribed by the concerned doctor. Self-medication without consulting a doctor may sometimes result in serious health implications.

• Never stop Aliskiren or change the dosage unless advised by the doctor.

• Fat-rich food negatively influences the Aliskiren absorption, hence patients are instructed to avoid such foodstuff while on treatment.

What Are the Possible Side Effects of Aliskiren?

• Diarrhea (loose stools) is the most widely reported side effect associated with Aliskiren. It is more frequently encountered in patients who are given a dose of 300 mg. Other gastrointestinal troubles like heartburn and stomach ache are also reported in some patients.

• Angioedema is a potentially serious side effect elicited by Aliskiren therapy. It is manifested in the form of a swollen and puffy face, neck, and head region. It eventually impedes the airflow leading to grave complications. Angioedema is precipitated as a result of exaggerated sensitivity to the drug. In certain patients, it leads to hoarseness of voice and trouble swallowing foodstuff.

• Cough is also reported occasionally upon Aliskiren intake. However, the underlying mechanism is still under discussion.

• Fainting is another major side effect of Aliskiren, indicating a considerable fall in blood pressure induced by the medicine.

What Should Be Done If a Dose Is Missed?

If a dose is missed by the patient unintentionally, then the patient is advised to take the tablet immediately once recalled. At times, patients may recall a missed dose only at the time of the next dose, in such cases, it is strongly advised not to administer twice the dose as prescribed by the doctor to balance the forgotten dose. Patients are asked to simply disregard the forgotten dose in such instances. Unnecessarily taking more than one dose that is suggested by the doctor may often result in other side effects and overdose issues. Therefore, patients are advised to strictly follow the doctor’s instructions.

How To Treat Aliskiren Overdose?

Aliskiren overdose is elicited most frequently in the form of fainting and collapse, which signifies a sudden drop in blood pressure (hypotension). Other critical symptoms like dizziness, increased tendency to vomit, and vague vision are also suggestive of an Aliskiren overdose. In the event of an overdose with hypotensive symptoms, prompt treatment intervention must be initiated at the earliest possible time.

How to Store Aliskiren Safely?

• Aliskiren comes in blister packaging as well as in bottles and stores it as such.

• Keep the medicine inaccessible to small children, otherwise, it could result in accidental self-administration by the child.

• Do not take medicines if they are out-of-date (expired).

• Set aside the medicine in a dry place to prevent moisture contamination.

• It is safe to keep the medicine within the normal room temperature range, not more than 30 degrees Celsius. Freezing the medicine may significantly impact the chemical structuring, and hence, it is strongly advised not to freeze.

For Doctors:

Indications:

Aliskiren is indicated for

• Hypertension.

• Cardiovascular disease (as an add-on).

Contraindications:

Aliskiren cannot be prescribed to all hypertensive patients. Contraindications of Aliskiren include the following:

• Pregnancy is a grave contraindication for Aliskiren, as it can cause significant deformations and even death of the fetus.

• Patients with a history of allergy or exaggerated sensitivity towards Aliskiren or its constituents.

• Newborn babies and children under the age of two.

• Known diabetic patients who are already under medication using ACEI or ARB.

• Severe renal diseases often precipitate renal failure upon Aliskiren administration, hence it is contraindicated.

Dosage and Administration:

• Dosing: The inceptive dose of 150 mg of Aliskiren once daily is advised for treating hypertension in adult patients. If the inceptive dose seems inadequate for tackling hypertension, then a 300 mg Aliskiren tablet is recommended. For younger patients in the age category of 6 to 17 years, the dose is determined by their body weight.

• Combination Therapy: Aliskiren is also prescribed as a combination therapy in association with other antihypertensive medicines like Calcium channel blockers and Angiotensin receptor blockers in the absence of underlying other disease conditions.

• Food Interaction: Routinely, Aliskiren does not interfere with the intake of food except fatty food. Fatty foods remarkably hold up the absorption of the drug.

Pharmacology

Mechanism of Action:

Aliskirenpotentially controls hypertension by directly checking renin. Renin holds the role of both enzyme and hormone and is chiefly produced by a group of kidney cells - juxtaglomerular cells. A remarkable reduction in renal perfusion and blood volume triggers the release of renin. It is essential for the breakdown of angiotensinogen into active angiotensin I. Further conversion of angiotensin I into angiotensin II is carried out by angiotensin-converting enzyme (ACE). Angiotensin II is well-known for its vasopressor effect. In addition, it induces the discharge of catecholamines and aldosterone. The reuptake of sodium is enhanced by angiotensin II. All these events contribute to a rise in blood pressure. But at the same time, angiotensin II elicits negative feedback towards a remarkable increase in blood pressure by checking the renin that is in charge of initiating the sequence of reactions. This is the mechanism by which blood pressure is regulated in a healthy human body in the absence of any external influence. In hypertensive patients, Aliskiren is advised, which holds back the renin and thus inhibits the cascade of events involved in blood pressure elevation.

Pharmacodynamics:

In addition to renin inhibition, Aliskiren brings down plasma renin activity (PRA). However, this pullback is independent of the dose of the drug administered.

Pharmacokinetics:

• Absorption: Once Aliskiren is administered orally, utmost absorption of the drug is reported within three hours. The utmost absorption of Aliskiren is estimated by assessing the plasma concentration of the drug. Aliskiren absorption is greatly affected when it is administered with fatty meals.

• Distribution: Aliskiren attains its maximal concentration in the plasma, usually in one to three hours after the oral intake of the drug.

• Metabolism: Almost 80 % of the Aliskiren in the plasma does not undergo any metabolism, while the remaining fraction undergoes oxidative metabolism in the liver. Cytochrome P450 3A4 (CYP3A4) is the chief enzyme that brings about the oxidative metabolism of Aliskiren.

• Excretion: Elimination of the Aliskiren drug molecule from the body happens primarily through the biliary or fecal route. However, a very small fraction of the unmetabolized Aliskiren is eliminated as such through urine.

Drug Interactions

Aliskiren exhibits significant interactions with the following drugs:

• Studies concluded that simultaneous administration of Aliskiren and Cyclosporin exaggerated and intensified the adverse reactions. Frequently encountered symptoms upon concurrent administration include severe gastrointestinal issues and hot flashes.

• The Pharmacokinetics and pharmacodynamics of Aliskiren are greatly modified by the simultaneous administration of itraconazole.

• In patients with weakened renal functions, parallel administration of Aliskiren along with non-steroidal anti-inflammatory agents (NSAIDs), particularly cyclooxygenase-2 inhibitors can precipitate renal failure. In addition, this interaction remarkably compromises the effectiveness of Aliskiren.

Warnings and Precautions Before Prescribing Aliskiren

• Lethal to Fetus: Aliskiren, when administered during pregnancy, may result in severe renal dysfunctions in the fetus, eventually giving rise to skeletal deformations, functional impairments, and at times even death of the fetus. Renal failure, skull hypoplasia, lung hypoplasia, and anuria develop due to the effect of Aliskiren on the fetus.

• Angioedema: Aliskiren administration, at times, may evoke swelling over the neck, face, and head region. Swelling is often reported in the lips, larynx, tongue, and glottis, which hamper the passage of air and precipitates respiratory blockage. Respiratory obstruction is life-threatening and necessitates immediate medical attention.

• Impact Renal Functions: Aliskerin therapy potentially enhances the likelihood of developing renal diseases, especially in patients with pre-existing renal conditions. Hence, it is advised to keep an eye on the patient’s renal functions while under Aliskiren.

• Pre-existing Diabetes: Aliskiren should not be given to diabetic patients receiving ACEI or ARB therapy, as it enhances the likelihood of developing renal failure.

• Hypotension: Certain patients receiving diuretics often elicit hypotension once Aliskiren therapy is started.

• Hyperkalemia: Special attention should be given to track the serum potassium level following Aliskiren administration. Diabetes, renal diseases, ARB, ACEI, diuretics, and NSAIDs act as potential triggers for hyperkalemia while on Aliskiren.

Other Specifications

Aliskiren During Pregnancy:

Aliskiren falls under category D among the pregnancy risk categories, which signify its harmful effect on the growing fetus. Potentially serious impacts on the fetus are reported when Aliskiren is administered, specifically in the last two trimesters of pregnancy. However, it is strongly advised to halt Aliskiren upon pregnancy detection.

Aliskiren During Breastfeeding:

There is no conclusive evidence concerning Aliskiren and breastfeeding. Certain animal studies proved that the Aliskiren drug discharges through breast milk. However, human studies are inconclusive, and at present, the drug is advised for a lactating mother considering the seriousness of the condition.

Aliskerin in Pediatric Patients:

Adequate information concerning the use of Aliskiren in small children is unavailable.