Monograph: |
Aliskiren
Pronunciation: (a-LIS-KYE-ren)
Class: Renin-angiotensin antagonist
Trade Names:
Tekturna
- Tablets 150 mg
- Tablets 300 mg
Pharmacology
Direct renin inhibitor, decreasing plasma renin activity and inhibiting conversion of angiotensinogen to angiotensin I.
All agents that inhibit the renin-angiotensin system suppress the negative feedback loop, leading to a compensatory rise in plasma renin concentration. Aliskiren blocks the clinical effect of increased renin levels.
Pharmacokinetics
Absorption
Bioavailability about 2.5%. Following oral administration, C max is reached within 1 to 3 h. High-fat meal decreases AUC and C max 71% and 85%, respectively. Steady-state blood levels reached in about 7 to 8 days. Accumulation t Β½ about 24 h.
Metabolism
Major enzyme responsible for aliskiren metabolism appears to be CYP3A4.
Elimination
About 25% of the absorbed dose of the parent drug appears to be excreted in the urine.
Hepatic or renal function impairment
Adjustment of the starting dose is not required.
Indications and Usage
Treatment of hypertension, either alone or in combination with other antihypertensive agents.
Contraindications
Standard considerations.
Dosage and Administration
Adults
PO Initial dose is 150 mg once daily. The daily dose may be increased to 300 mg in patients whose BP is not adequately controlled.
General Advice
Β· May be taken without respect to meals.
Drug Interactions
ACE inhibitors (eg, captopril)
Risk of hyperkalemia may be increased.
Atorvastatin
Aliskiren C max and AUC may be increased about 50%.
Furosemide
Blood concentrations may be reduced by aliskiren, decreasing furosemide efficacy.
Irbesartan
Aliskiren C max may be reduced up to 50%.
Ketoconazole
Aliskiren plasma concentrations may be increased.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Dermatologic
Rash (1%)
GI
Diarrhea (2%).
Lab Tests
Elevated BUN or serum creatinine (less than 7%); increased creatine kinase (1%).
Respiratory
Increased cough (1%).
Miscellaneous
Angioedema (0.06%).
Precautions
Warnings Use during the second and third trimesters can cause injury and death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.
Pregnancy
Category C (first trimester); Category D (second and third trimesters).
Lactation
Undetermined.
Children
Safety and efficacy not established.
Amniotic fluid
In rare instances, when no alternative therapy was available, use in pregnancy has been associated with amniotic fluid deficiency.
Angioedema
Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported and may occur any time during treatment.
Hypotension
Rarely, excessive fall in BP may occur.
In-utero exposure
Closely observe infants for hypotension, oliguria, and hyperkalemia.
Overdosage
Symptoms
Possible hypotension.
Patient Information
Β· Inform female patients of childbearing potential of the risk associated with aliskiren exposure during the second and third trimesters of pregnancy.
Β· Advise patient to immediately report swelling of the face, extremities, eyes, lips, or tongue, or difficulty in swallowing or breathing to health care provider and not to take another dose until doing so.
|