ALISKIREN HEMIFUMARATE
Clinical safety rating
cautionComprehensive clinical and safety monograph for ALISKIREN HEMIFUMARATE (ALISKIREN HEMIFUMARATE).
Direct renin inhibitor that binds to the active site of renin, blocking the conversion of angiotensinogen to angiotensin I, thereby reducing angiotensin II levels and decreasing vasoconstriction and aldosterone secretion.
| Metabolism | Primarily metabolized by CYP3A4; also undergoes O-demethylation and glucuronidation. Aliskiren is a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily hepatic metabolism via CYP3A4, with unchanged drug excreted in feces (91%) and urine (<1% unchanged). Biliary excretion accounts for a minor fraction; approximately 1.4% of the dose is recovered unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 23–24 hours in healthy subjects, allowing once-daily dosing. In patients with renal impairment (CrCl <30 mL/min), half-life may be prolonged to ~40 hours. |
| Protein binding | Moderate protein binding: approximately 49–50% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 1.5 L/kg, indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Oral bioavailability is low, approximately 2–3% due to incomplete absorption and extensive first-pass metabolism by CYP3A4. |
| Onset of Action | Onset of antihypertensive effect occurs within 1–2 hours after oral administration; peak effect is seen at 4–6 hours. |
| Duration of Action | Duration remains effective for 24 hours with once-daily dosing; sustained blood pressure reduction is maintained over the dosing interval. Some effect may persist for up to 48 hours. |
| Molecular Weight | 551.63 Da |
150 mg orally once daily; may increase to 300 mg once daily if blood pressure not controlled.
| Dosage form | TABLET |
| Renal impairment | eGFR <30 mL/min/1.73 m²: contraindicated. eGFR 30–59: no adjustment. |
| Liver impairment | Child-Pugh A, B, C: no adjustment required as pharmacokinetics are not significantly altered. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; start at 150 mg daily due to potential greater hypotensive effect. |
| 1st trimester | Aliskiren is contraindicated in pregnancy. Data from animal studies and human experience suggest fetotoxicity and potential teratogenicity. Use is not recommended during the first trimester. |
| 2nd trimester | Aliskiren is contraindicated in the second trimester due to risk of fetal renal dysfunction, oligohydramnios, and skull ossification defects. Alternative antihypertensives should be used. |
| 3rd trimester | Aliskiren is contraindicated in the third trimester due to risks of fetal renal impairment, oligohydramnios, and neonatal hypotension. Avoid use. |
Clinical note
Comprehensive clinical and safety monograph for ALISKIREN HEMIFUMARATE (ALISKIREN HEMIFUMARATE).
| Placental transfer | Animal studies indicate that aliskiren crosses the placenta and accumulates in fetal tissues. In humans, placental transfer is likely given molecular weight and pharmacological properties, but specific quantitative data are lacking. |
| Breastfeeding | Aliskiren is excreted into breast milk in animal studies; human data are not available. Due to potential for adverse effects in the nursing infant, breastfeeding is generally not recommended during therapy. Consider alternative agents with a more established safety profile in lactation. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | Pregnancy category D: Risk of fetal renal dysfunction, oligohydramnios, skull ossification defects, and neonatal morbidity/mortality. Avoid in second and third trimesters due to renin-angiotensin system blockade. First trimester exposure is not associated with major teratogenic risk but use is still cautioned. |
| Fetal Monitoring | Monitor maternal blood pressure, serum creatinine, potassium, and urine output. Serial ultrasound for fetal growth, amniotic fluid volume (oligohydramnios), and kidney morphology. Fetal echocardiography recommended due to possible cardiac effects. |
| Fertility Effects | No known direct effects on fertility in animal studies. Indirect effects may occur via renin-angiotensin system blockade impacting ovarian function or implantation, but human data are lacking. |
■ FDA Black Box Warning
Do not use in pregnancy. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected.
| Serious Effects |
PregnancyHistory of angioedema with previous aliskiren useConcurrent use with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in patients with diabetes mellitus (due to increased risk of renal impairment, hypotension, and hyperkalemia)
| Precautions | Fetal toxicity (boxed warning), Hypotension in volume-depleted patients, Renal impairment: monitor renal function, Hyperkalemia: increased risk with diabetes, renal impairment, or concomitant use of ACE inhibitors or ARBs, Angioedema: rare but serious |
| Food/Dietary | High-fat meals significantly reduce aliskiren absorption (up to 70% decrease in Cmax and AUC). It is recommended to take aliskiren consistently either with or without food, but avoid a high-fat meal close to dosing. Grapefruit juice may slightly decrease aliskiren exposure; clinical significance is minimal but consider avoiding. No other significant food interactions. |
| Clinical Pearls | Aliskiren is a direct renin inhibitor used for hypertension. It should not be combined with ACE inhibitors or ARBs in patients with diabetes or renal impairment (eGFR <60 mL/min). Monitor renal function and potassium levels due to risk of hyperkalemia. Avoid in pregnancy (category X) and severe renal impairment. Aliskiren's antihypertensive effect may be reduced by high-fat meals; take consistently with or without food. |
| Patient Advice | Take aliskiren exactly as prescribed, usually once daily. · Avoid high-fat meals close to dosing time as they reduce absorption. · Do not stop taking this medication abruptly without consulting your doctor. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Report symptoms such as dizziness, fainting, irregular heartbeat, or muscle weakness. · Avoid salt substitutes containing potassium and potassium supplements without medical advice. · Keep all appointments for blood pressure and lab tests (potassium, renal function). |
Loading safety data…