Aliskiren (Tekturna):INDICATIONS, USAGE, and DOSAGE FORMS ||

Aliskiren (Tekturna)

DOSAGE FORMS AND STRENGTHS

150 mg light pink biconvex round tablet.

300 mg light red biconvex ovaloid round tablet.

INDICATIONS AND USAGE

Hypertension

Tekturna (Aliskiren) is utilized for treating hypertension, with the goal of lowering blood pressure. The reduction of blood pressure is associated with a decreased risk of both fatal and nonfatal cardiovascular events, particularly strokes and myocardial infarctions. These benefits have been noted in controlled trials of antihypertensive drugs from a diverse range of pharmacologic classes. However, there are no controlled trials that establish risk reduction with Tekturna.

Effective management of high blood pressure should be part of a comprehensive cardiovascular risk management approach, which may include, as necessary, lipid control, diabetes management, antithrombotic therapy, smoking cessation, physical activity, and restricted sodium intake. Many patients may require multiple medications to achieve their blood pressure targets. For tailored advice on goals and management, refer to the published guidelines, such as those from the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

A wide range of antihypertensive medications, belonging to various pharmacological classes and operating through different mechanisms, have demonstrated their ability to decrease cardiovascular morbidity and mortality in randomized controlled trials. It can be inferred that the primary factor contributing to these benefits is the reduction of blood pressure, rather than any other pharmacological characteristic of the medications. The most significant and consistent cardiovascular outcome benefit observed has been a decrease in the risk of stroke; however, there have also been frequent observations of reductions in myocardial infarction and cardiovascular mortality.

Some antihypertensive medications exhibit reduced blood pressure effects (when used alone) in black patients, and numerous antihypertensive drugs possess further approved indications and effects (such as those related to angina, heart failure, or diabetic kidney disease). These factors may influence the choice of therapy.

DOSAGE AND ADMINISTRATION

Hypertension

The standard initial dosage of Aliskiren is 150 mg taken once daily. For patients whose blood pressure remains inadequately controlled, the daily dosage may be raised to 300 mg. Doses exceeding 300 mg did not produce a greater response in blood pressure but led to a higher incidence of diarrhea. The antihypertensive effect of a specific dosage is largely achieved (85-90%) within 2 weeks.

Use with Other Antihypertensive

Tekturna (Aliskiren) may be used in conjunction with certain other antihypertensive agents. For diabetic patients, it is not recommended to use it in combination with angiotensin receptor blockers (ARBs) or angiotensin converting enzyme inhibitors (ACEIs). The simultaneous administration of aliskiren with an ARB or ACEI is not advisable for patients with a GFR of less than 60 ml/min. Most of the current experience involves diuretics, an angiotensin receptor blocker (valsartan), or a calcium channel blocker (amlodipine). The combination of aliskiren with these drugs yields a more pronounced effect at their maximum recommended doses than either agent alone. It is not established whether there are additive effects when Tekturna is utilized with angiotensin-converting enzyme inhibitors (ACEIs) or beta blockers (BB).

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CONTRAINDICATIONS

Do not use aliskiren with ARBs or ACEIs in patients with diabetes.

WARNINGS AND PRECAUTIONS

Fetal Toxicity:

Pregnancy Category D

The use of medications that affect the renin-angiotensin system in the second and third trimesters of pregnancy is associated with a reduction in fetal renal function and an increase in morbidity and mortality rates for both the fetus and the neonate. Oligohydramnios that results can be correlated with fetal lung hypoplasia and skeletal deformities. Potential adverse effects for neonates may include skull hypoplasia, anuria, hypotension, renal failure, and death. Discontinuation of Tekturna is advised once pregnancy is confirmed.

Renal Impairment/Hyperkalemia/Hypotension when Tekturna is given in combination with ARBs or ACEI

Tekturna(Aliskiren) is not recommended for patients with diabetes who are taking ARBs or ACE inhibitors due to the heightened risk of renal impairment, hyperkalemia, and hypotension.

Avoid use of Aliskiren with ARBs or ACEI in patients with moderate renal impairment (GFR <60 ml/min).

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Head and Neck Angioedema

Angioedema of the face, limbs, lips, tongue, glottis, and/or larynx has been documented in individuals treated with Aliskiren, resulting in the need for hospitalization and intubation. This can happen at any stage of treatment and has been reported in patients with or without a history of angioedema associated with ACE inhibitors or angiotensin receptor antagonists. If angioedema affects the throat, tongue, glottis, or larynx, or if the patient has a history of upper respiratory surgery, there is a potential for airway obstruction, which may be life-threatening. Patients who experience these symptoms, even in the absence of respiratory distress, require careful monitoring, as antihistamines and corticosteroids may not be sufficient to prevent respiratory involvement. Rapid administration of subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 ml) and measures to ensure an open airway may be essential.

Immediately discontinue Aliskiren in patients who show signs of angioedema, and do not administer it again.

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Hypotension

In individuals with an activated renin-angiotensin system, particularly those who are volume- and/or salt-depleted (for instance, patients on high doses of diuretics), symptomatic hypotension may arise following the commencement of treatment with Tekturna. This condition must be addressed before the administration of Tekturna, or the treatment should be initiated under stringent medical supervision.

A temporary hypotensive reaction does not preclude the continuation of treatment, which can typically proceed without complications once blood pressure has stabilized.

Impaired Renal Function

It is essential to periodically monitor renal function in patients undergoing treatment with Tekturna. Medications that influence the renin-angiotensin system can lead to alterations in renal function, including the potential for acute renal failure. Patients whose renal function may be partially reliant on the renin-angiotensin system (for instance, those with renal artery stenosis, severe heart failure, post-myocardial infarction, or volume depletion) or those receiving ARB, ACEI, or non-steroidal anti-inflammatory (NSAID) medications may face an increased risk of experiencing acute renal failure while on Tekturna.

Hyperkalemia

It is essential to periodically monitor serum potassium levels in patients who are being treated with Tekturna. Medications that influence the renin-angiotensin system may lead to hyperkalemia. Factors that increase the risk of developing hyperkalemia include renal insufficiency, diabetes, concurrent use of ARBs or ACE inhibitors, NSAIDs, potassium supplements, or potassium-sparing diuretics.

Cyclosporine or Itraconazole

When aliskiren was given with cyclosporine or Itraconazole, the blood concentrations of aliskiren were significantly increased. Avoid concomitant use of aliskiren with cyclosporine or Itraconazole.

ADVERSE REACTIONS

Clinical Trials Experience

Given that clinical trials are performed under a range of differing conditions, the rates of adverse reactions noted in the clinical trials of one drug cannot be directly compared to those of another drug and may not accurately reflect the rates observed in real-world practice.

The information detailed below reflects the safety evaluation of Tekturna involving more than 6,460 patients, including over 1,740 who were treated for more than 6 months, and more than 1,250 patients treated for over 1 year. In clinical trials that were placebo-controlled, the discontinuation of therapy due to a clinical adverse event, including uncontrolled hypertension, occurred in 2.2% of patients treated with Tekturna versus 3.5% of patients receiving placebo. This data does not include findings from the ALTITUDE study, which assessed the use of aliskiren in combination with ARBs or ACEI.

Angioedema: In clinical studies, two instances of angioedema accompanied by respiratory symptoms were documented in patients using Tekturna. Additionally, two other instances of periorbital edema, which did not present respiratory symptoms, were noted as potential angioedema cases, leading to treatment discontinuation. The occurrence rate of these angioedema cases in the completed studies was recorded at 0.06%. Furthermore, there were 26 additional reports of edema affecting the face, hands, or entire body associated with Tekturna use, with four cases resulting in discontinuation. In placebo-controlled studies, the incidence of edema affecting the face, hands, or entire body was 0.4% for Tekturna, compared to 0.5% for the placebo group. In a long-term active control study involving both Tekturna and HCTZ treatment arms, the incidence of edema affecting the face, hands, or entire body was consistently 0.4% across both treatment groups.

Clinical Laboratory Findings

In controlled clinical trials, significant alterations in standard laboratory parameters were infrequently linked to the administration of Tekturna in patients with hypertension who were not simultaneously treated with an ARB or ACEI. In multiple-dose studies involving hypertensive patients, Tekturna did not exhibit any clinically significant effects on total cholesterol, HDL, fasting triglycerides, or fasting glucose.

Blood Urea Nitrogen, Creatinine: Among patients with hypertension not treated concurrently with an ARB or ACEI, slight increases in blood urea nitrogen (BUN) or serum creatinine were noted in fewer than 7% of patients receiving Tekturna alone compared to 6% on placebo [refer to Warnings (5.2)].

Hemoglobin and Hematocrit: Minor reductions in hemoglobin and hematocrit (average decreases of about 0.08 g/dL and 0.16 volume percent, respectively, for all aliskiren monotherapy) were recorded.

Serum Potassium: In patients with hypertension not concomitantly treated with an ARB or ACEI, increases in serum potassium >5.5 mEq/L were infrequent (0.9% compared to 0.6% with placebo).

DRUG INTERACTIONS

Cyclosporine: It is advised to avoid the co-administration of cyclosporine with aliskiren.

Itraconazole: It is recommended to refrain from co-administering Itraconazole with aliskiren.

Non-Steroidal Anti-Inflammatory Agents (NSAIDs), including selective Cyclooxygenase-2 inhibitors (COX-2 inhibitors): In elderly patients, those who are volume-depleted (including individuals undergoing diuretic therapy), or those with impaired renal function, the co-administration of NSAIDs, including selective COX-2 inhibitors, with agents that influence the renin-angiotensin system, such as aliskiren, may lead to a decline in renal function, potentially resulting in acute renal failure. These effects are generally reversible. It is important to monitor renal function periodically in patients who are receiving both aliskiren and NSAID therapy.

The antihypertensive effect of aliskiren may be diminished by NSAIDs.

USE IN SPECIFIC POPULATIONS

I. Pregnancy

Pregnancy Category D

The administration of medications that influence the renin-angiotensin system during the second and third trimesters of pregnancy can impair fetal renal function and elevate the risks of morbidity and mortality in both the fetus and neonate. The resultant oligohydramnios may lead to complications such as fetal lung hypoplasia and skeletal deformities. Possible adverse effects in neonates include skull hypoplasia, anuria, hypotension, renal failure, and even death. Upon confirmation of pregnancy, it is imperative to cease the use of Tekturna at the earliest opportunity. These negative outcomes are typically linked to the use of such medications during the second and third trimesters of pregnancy. Most epidemiological research investigating fetal abnormalities following exposure to antihypertensive medications in the first trimester has not differentiated between drugs that affect the renin-angiotensin system and other antihypertensive drugs. Effective management of maternal hypertension throughout pregnancy is crucial to ensure optimal outcomes for both the mother and the fetus.

In the rare instance that there is no suitable alternative to pharmacological therapy targeting the renin-angiotensin system for a specific patient, inform the mother about the potential risks to the fetus. Conduct serial ultrasound examinations to evaluate the intra-amniotic environment. Should oligohydramnios be detected, cease the use of Tekturna, unless it is deemed essential for the mother's survival.

Fetal testing may be warranted, depending on the gestational week. It is important for both patients and healthcare providers to recognize that oligohydramnios may not manifest until after the fetus has experienced irreversible damage.

ii. Nursing Mothers

It remains uncertain whether aliskiren is present in human breast milk. Aliskiren has been found in the milk of lactating rats.

Due to the potential risks to the nursing infant, a decision must be made regarding the continuation of breastfeeding or the discontinuation of the medication, considering the significance of the drug for the mother.

iii. Pediatric Use

The safety and efficacy of aliskiren in pediatric patients under 18 years of age have not been determined.

For neonates with a history of in utero exposure to Tekturna:

If oliguria or hypotension arises, focus on supporting blood pressure and renal perfusion. Exchange transfusions or dialysis may be necessary to address hypotension and/or to compensate for impaired renal function.

iv. Geriatric Use

Of the total number of patients who participated in clinical studies involving aliskiren, 1,275 (19%) were aged 65 years or older, while 231 (3.4%) were aged 75 years or older. No significant differences in safety or effectiveness were noted between these older patients and their younger counterparts. Additionally, other clinical experiences have not revealed any discrepancies in responses between elderly and younger patients, although it is important to acknowledge that some older individuals may exhibit greater sensitivity.

V. Renal impairment

The safety and effectiveness of Tekturna in patients with severe renal impairment (CrCL <30 ml/min) have not been determined, as individuals with eGFR <30ml/min were excluded from clinical trials.

OVERDOSAGE

Limited information exists regarding overdosage in humans. The most probable indication of overdosage would be hypotension. Should symptomatic hypotension arise, supportive care should be commenced.

Aliskiren is not effectively removed by dialysis. Consequently, hemodialysis is insufficient for managing aliskiren overexposure.