Aliskiren

Indications

Aliskiren is used for: Hypertension

Adult Dose

Oral Essential hypertension Adult: >18 yr 150 mg once daily, increased to 300 mg once daily if needed. Elderly: No dosage adjustment needed. Hepatic impairment: No dosage adjustment needed.

Child Dose

Renal Dose

Renal Impairment Mild to moderate: No dosage adjustment needed. Severe: Contraindicated.

Administration

Administration May be taken with or without food. Take consistently w/ or w/o meals. Avoid taking w/ high fat meals.

Contra Indications

History of angioedema; severe renal impairment. Concomitant use w/ ACE inhibitors or angiotensin II receptor antagonists in patients w/ DM and renal impairment (GFR <60 mL/min). Concomitant use w/ ciclosporin, itraconazole and quinidine. Pregnancy.

Precautions

Serious CHF, sodium or volume depletion. Discontinue if diarrhoea is severe and persistent. Lactation. Monitoring Parameters Periodically monitor serum potassium concentration and renal function. Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death. Lactation: Excretion in milk unknown/not recommended.

Pregnancy-Lactation

Pregnancy Fetal harm may occur when administered to a pregnant woman Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (eg, need for cesarean section, and post-partum hemorrhage); hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death Fetal or neonatal adverse reactions Use of drugs that act on the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, oligohydramnios, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death Perform serial ultrasound examinations to assess the intra-amniotic environment Observe infants with histories of in utero exposure to aliskiren for hypotension, oliguria, and hyperkalemia; if oliguria or hypotension occur in neonates with a history of in utero exposure to aliskiren, support blood pressure and renal perfusion Lactation There is no information regarding the presence of aliskiren in human milk, the effects on the breastfed infant, or the effects on milk production Owing to the potential for serious adverse reactions, including hypotension, hyperkalemia and renal impairment in nursing infants Advise a nursing woman that breastfeeding is not recommended during therapy

Interactions

Increased risk of hypotension w/ other antihypertensives. Increased risk of acute renal failure w/ ACE inhibitors, angiotensin II receptor antagonists or NSAIDs. Antihypertensive effect may be reduced w/ NSAIDs. Increased serum levels w/ atorvastatin, itraconazole, ketoconazole, verapamil. Significant decrease in furosemide concentrations w/ aliskiren. Increased risk of hyperkalaemia w/ potassium-sparing diuretics, potassium supplements or any substances that may increase serum potassium levels. Potentially Fatal: Increased risk of renal impairment, hypotension and hyperkalaemia w/ ACE inhibitors or angiotensin II receptor antagonists. Markedly increased plasma concentration w/ ciclosporin, itraconazole and quinidine.

Adverse Effects

Side effects of Aliskiren : 1-10% Diarrhea (2.3%), Cough (1.1%), Rash (1%), Increase in serum creatinine (<7%), Hyperkalemia (<1%) <1% Angioedema, Headache, Gout, Renal stones, Seizure, Severe hypotension, Rhabomyolysis, Toxic epidermal necrolysis, Increase in uric acid, Angina Potentially Fatal: Anaphylactic reactions.

Mechanism of Action

Aliskiren is an orally active, potent, non-peptide and selective direct renin inhibitor used in the management of HTN. By inhibiting the enzyme renin, it prevents conversion of angiotensinogen into angiotensin I and therefore inhibits subsequent production of angiotensin II and aldosterone. Unlike ACE inhibitors and angiotensin II receptor antagonists which cause a compensatory rise in plasma renin activity, treatment w/ aliskiren decreases plasma renin activity and concentrations of angiotensin I, angiotensin II and aldosterone .