Pbm-map drug Monograph: Aliskiren




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FDA Approved Indication(s) and Off-Label Uses1,2



Aliskiren is FDA approved for the treatment of patients with HTN. Aliskiren may be used as monotherapy or in combination with other antihypertensive agents. Clinical trials including patients with heart failure, post myocardial infarction, left ventricular hypertrophy, diabetes mellitus and proteinuria, diabetic nephropathy, and in the elderly are ongoing or have recently been completed.

Current VA National Formulary Alternatives





Thiazides

ACEIs

Long-Acting CCBs

Beta-blockers

Supplemental Agents*

Chlorthalidone

Hydrochlorothiazide (HCTZ)

Indapamide

HCTZ/triamterene



Benazepril

Captopril

Enalapril

Fosinopril

Lisinopril


Amlodipine

Felodipine

Nifedipine

Diltiazem

Verapamil


Atenolol

Metoprolol

Propranolol


Clonidine

Doxazosin

Hydralazine

Methyldopa

Minoxidil

Prazosin


Reserpine

Spironolactone

Terazosin


*ARBs are restricted to criteria for use and may be considered in patients who are ACEI intolerant; alpha1-blockers are not recommended as monotherapy for the treatment of HTN; loop diuretics are generally not recommended for the treatment of HTN

Dosage and Administration1,2



General Recommendations: Aliskiren is administered once daily. It is recommended that aliskiren be taken consistently with regard to mealtime as high fat meals decreased absorption of the drug.

Availability

Initial Dose

Titration Interval

Maximum Dose

Comments

150 mg

300 mg


film-coated

tablets


150 mg once daily

Increase to 300mg once daily at 2 weeks (85-90% of response seen by 2 weeks)

300 mg once daily

(↑ diarrhea with higher doses, without improved BP control)



No dose adjustments necessary in elderly, or in patients with renal or hepatic impairment; caution in severe renal disease due to limited data


Adverse Events1,2,7,8
Aliskiren is generally well-tolerated. Discontinuation due to an adverse event was reported in 2.2% of patients receiving aliskiren compared to 3.5% on placebo.
Two cases of angioedema with respiratory symptoms and two cases of periorbital edema without respiratory symptoms were reported with aliskiren in clinical trials (0.06% patients). Edema involving the face, hands, or entire body was reported in 26 additional cases of patients taking aliskiren (4 patients discontinued therapy). Edema (involving the face, hands, or entire body) was reported in 0.4% of patients on aliskiren compared to 0.5% of patients on placebo. There were no reports of angioedema in the published comparison trials of aliskiren with an ACEI or an ARB. The incidence of angioedema in patients taking an ACEI is reported to be approximately 0.1-1.2%. There has also been a number of published case reports of angioedema in patients treated with an ARB. In approximately one third of these cases, the patients previously experienced angioedema with an ACEI.
The manufacturer states that in comparison trials with an ACEI, the incidence of cough with aliskiren was reported to be ~33%-50% of that reported with the ACEIs. In a clinical trial comparing the tolerability of aliskiren and lisinopril in patients with severe HTN, cough was reported in 0.8% of patients in the aliskiren treatment group and in 1.7% of patients who received lisinopril.7 Another trial comparing aliskiren to ramipril reported cough in 2.1% of patients on aliskiren, 4.7% of patients on ramipril, and 1.8% of the patients receiving combination therapy with the two agents.2
Unpublished results from long-term studies of therapy (26 weeks) with aliskiren reported serious adverse events in 1.9% of patients on aliskiren compared to 1.4% of patients receiving ramipril.2 In another unpublished long-term comparison trial (12 months duration) of over 1900 patients, it was reported that 5.1% of patients randomized to aliskiren 150 mg, 4.3% to aliskiren 300 mg, 5% on monotherapy, and 4.5% on combination therapy with hydrochlorothiazide experienced serious adverse events; including, cerebrovascular event (5 patients), acute myocardial infarction (4 patients), HTN (3 patients), hypertensive crisis (3 patients). Six patients had a serious adverse event that was thought to be drug-related (treatment group or adverse event not reported). Discontinuations due to adverse events occurred in 5.9% of patients on aliskiren 150 mg and 5.3% of patients randomized to treatment with aliskiren 300 mg.2

Dose related increases in diarrhea have been reported in patients overall at 300mg (2.3%), with rates in older patients (> 65 years) and females at the 150mg dose comparable to the 300mg dose in men or younger patients. Two patients treated with aliskiren experienced an episode of tonic-clonic seizures with loss of consciousness (one patient was predisposed to seizures); treatment was discontinued in these patients.


The most frequently occurring adverse events (reported in > 1% of patients receiving aliskiren with similar or greater incidence in patients on placebo) included: headache, nasopharyngitis, dizziness, fatigue, upper respiratory tract infection, back pain, cough. The frequency of headache and nasopharyngitis reported in a pooled analysis of 7,060 patients enrolled in seven randomized controlled trials is shown in the table below (Novartis, Data on File;2 also refer to reports of most frequently reported adverse events in the clinical trial data compiled in Appendices 1-3).

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