Aliskiren hemifumarate + Hydrochlorothiazide

Treatment of essential hypertension in adults. Indicated in patients whose blood pressure is not adequately controlled on aliskiren or hydrochlorothiazide used alone. Indicated as substitution therapy in patients adequately controlled with aliskiren and hydrochlorothiazide, given concurrently, at the same dose level as in the combination.

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 with aliskiren decreases plasma renin activity and concentrations of angiotensin I angiotensin II and aldosterone .
 
Hydrochlorothiazide inhibits the reabsorption of Na and Cl in the distal tubules causing increased excretion of Na and water K and hydrogen ions.

The recommended dose is one tablet per day. The antihypertensive effect is largely manifested within 1 week and the maximum effect is generallyseen within 4 weeks

1. 150 mg/12.5 mg may be administered in patients whose blood pressure is not adequatelycontrolled with Aliskiren 150 mg or Hydrochlorothiazide 12.5 mg alone.
2. 150 mg/25 mg may be administered in patients whose blood pressure is not adequately controlled with Aliskiren 150 mg or Hydrochlorothiazide 25 mg alone or by Aliskiren + Hydrochlorothiazide 150 mg/12.5 mg.
3. 300 mg/12.5 mg may be administered in patients whose blood pressure is not adequately controlled with Aliskiren 300 mg or Hydrochlorothiazide 12.5 mg alone or by Aliskiren + Hydrochlorothiazide150 mg/12.5 mg.
4. 300 mg/25 mg may be administered in patients whose blood pressure is not adequately controlled with Aliskiren 300 mg or Hydrochlorothiazide 25 mg alone or by Aliskiren + Hydrochlorothiazide 300 mg/12.5 mg or 150 mg/25 mg.
5. If blood pressure remains uncontrolled after 2-4 weeks of therapy, the dose may be titrated up to a maximum of Aliskiren + Hydrochlorothiazide 300 mg/25 mg daily. Dosing should be individualised and adjusted according to the patient’s clinical response.

Aliskiren increased risk of hypotension with other antihypertensives. Increased risk of acute renal failure with ACE inhibitors, angiotensin II receptor antagonists or NSAIDs. Antihypertensive effect may be reduced with NSAIDs. Increased serum levels with atorvastatin, itraconazole, ketoconazole, verapamil. Significant decrease in furosemide concentrations with aliskiren. Increased risk of hyperkalaemia with potassium-sparing diuretics, potassium supplements or any substances that may increase serum potassium levels.

Potentially Fatal: Increased risk of renal impairment, hypotension and hyperkalaemia with ACE inhibitors or angiotensin II receptor antagonists. Markedly increased plasma concentration with ciclosporin, itraconazole and quinidine.

Hydrochlorothiazide increases toxicity of lithium. May potentiate orthostatic hypotension with barbiturates and narcotics. Enhanced neuromuscular blocking action of competitive neuromuscular blockers (e.g. atracurium). Increased hypokalaemic effect with corticosteroids, corticotropin, beta 2 agonists (e.g. salbutamol). Additive effect with other antihypertensives. Potentiation of orthostatic hypotension with 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.

1. Hypersensitivity to the active substances
2. History of angioedema with aliskiren.
3. Hereditary or idiopathic angioedema.
4. Second and third trimesters of pregnancy
5. Anuria.
6. Hyponatraemia, hypercalcaemia, symptomatic hyperuricaemia and refractory hypokalaemia.
7. Severe hepatic & renal impairment.
8. The concomitant use of Aliskiren & Hydrochlorothiazide with an ACEI or an ARB is contraindicated in patients with diabetes mellitus or renal impairment

Dizziness,Vertigo,Hypokalemia,Increased uric acid level ,Hyperkalemia, Diarrhea, Increased ALT , Flu-like syndrome, Cough, Weakness, Arthralgia, Diarrhea, Cough, Rash, Increased creatinine kinase, Increased BUN, Hyperkalemia, Decreased hematocrit, Decreased hemoglobin Aliskiren, Gastroesophageal reflux, Periorbital edema, Toxic epiderma necrolysis, Increased uric acid, Severe hypotension, Stevens Johnson syndrome

Pregnancy Category-D. Enters in breast milk; Not recommended