Aliskiren Hemifumarate + Hydrochlorothiazide

Indications

Aliskiren Hemifumarate + Hydrochlorothiazide is used for: Hypertension

Adult Dose

Adult: PO Hypertension Add-on or initial therapy: Initiate with 12.5 mg/150 mg PO qDay; after 2-4 weeks, may increase dose if needed; not to exceed 25 mg/300 mg Hepatic Impairment Dose adjustment not necessary

Child Dose

Renal Dose

Renal Impairment CrCl <30 mL/min: Use with caution >30 mL/min: Dose adjustment not necessary

Administration

Administration May be taken with or without food.

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: enters breast milk; not recommended.

Pregnancy-Lactation

Pregnancy Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly Aliskiren Use of drugs that act on renin-angiotensin system in second and third trimesters of pregnancy can result in reduced fetal renal function leading to anuria and renal failure, oligohydramnios, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death In patients taking this combination drug during pregnancy, perform serial ultrasound examinations to assess intra-amniotic environment; fetal testing may be appropriate, based on the week of gestation; patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury; closely observe infants with histories of in utero exposure to the drug combination for hypotension, oliguria, and hyperkalemia; if oliguria or hypotension occur in neonates with a history of in utero exposure to the drug combination, support blood pressure and renal perfusion; exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function Lactation Limited published studies report that hydrochlorothiazide is present in human milk; however, there is insufficient information to determine the effects hydrochlorothiazide on the breastfed infant or effects of hydrochlorothiazide on milk production; because of potential for serious adverse reactions, including hypotension, electrolyte imbalances and renal impairment in nursing infants, advise a nursing woman that breastfeeding is not recommended during therapy

Interactions

Aliskiren 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. Hydrochlorothiazide increases toxicity of lithium. May potentiate orthostatic hypotension w/ barbiturates and narcotics. Enhanced neuromuscular blocking action of competitive neuromuscular blockers (e.g. atracurium). Increased hypokalaemic effect w/ corticosteroids, corticotropin, beta 2 agonists (e.g. salbutamol). Additive effect w/ other antihypertensives. Potentiation of orthostatic hypotension w/ barbiturates or opioids. Reduced antihypertensive effect by drugs that cause fluid retention (e.g. corticosteroids, NSAIDs, carbenoxolone). Enhanced nephrotoxicity of NSAIDs. Reduced therapeutic effect of antidiabetics.

Adverse Effects

Side effects of Aliskiren Hemifumarate + Hydrochlorothiazide : >10% Increased BUN 1-10% Dizziness (2%), Vertigo (1%), Hypokalemia (2%), Increased uric acid level (2%), Hyperkalemia (1%), Diarrhea (2%), Increased ALT (1%), Flu-like syndrome (2%), Cough (1%), Weakness (1%), Arthralgia (1%) Aliskiren Diarrhea (2.3%), Cough (1.1%), Rash (1%), Increased creatinine kinase (1%), Increased BUN (≤ 7%), Hyperkalemia (≤1%) <1% Decreased hematocrit, Decreased hemoglobin Aliskiren Gastroesophageal reflux, Periorbital edema, Toxic epiderma necrolysis, Increased uric acid, Severe hypotension, Stevens Johnson syndrome 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 . Hydrochlorothiazide inhibits the reabsorption of Na and chloride in the distal tubules causing increased excretion of Na and water K and hydrogen ions.