Tekturna HCT

Product
Tekturna HCT

Approval Date
January 21, 2008

Release Date
February 29, 2008

Company
Novartis

Class
Antihypertensive (direct renin inhibitor + thiazide)

Indication
Hypertension

Active Ingredient
Aliskiren 150mg, hydrochlorothiazide (HCTZ) 12.5mg; tabs.

Agency Roster
Integrated Communications Corp. (Professional)
Deutsch (DTC)

MarketingStrategy/Execution
The first fixed-dose combination involving Novartis’first-in-class oral renin inhibitor, Tekturna with hydrochlorothiazide (HCT)was approved in the USin January 2008. A single-tablet combination with a diuretic, it follows thelaunch in March 2007 of Tekturna (aliskiren), which has since rung up sales of$40 million.The Swiss firm is operating leaner than usual, having trimmed thesize of its US pharma field force last year by 430 reps, to 6,400. For certainproducts, personal selling is complemented by television, newspaper andmagazine ads, as well as online direct marketing. For instance, the “BP SuccessZone” e-marketing program—already used with Novartis high-blood-pressure pill Diovan—is featured on theTekturna.com microsite. Novartis hopes patients view Tekturna HCT as a simplerway of controlling hypertension. Rasilez HCT, the combo drug’s ex-US name, hasbeen submitted in other countries, including the EU, and additional filings ofother fixed-dose combination products are planned for 2008-2010.

The Market

Also in the Pipeline(according to Adis R&D Insight)
No competitor products in phase III or pre-registration, US.

Physician Outlook
Tekturna HCT is the latest hydrochlorothiazide combinationanti-hypertensive to enter this market; but what makes this product unique isthat it is the first one associated with a direct renin inhibitor, i.e.Tekturna (aliskerin). Novartis’ collaboration with Speedel, whichdeveloped the molecule, culminated in 2007, when it launched the first newclass of antihypertensives to be introduced in many years. Research amongphysicians confirms the continued need for high blood pressuretreatments: the data show that blood pressure goals are not reached inroughly one third of patients who begin monotherapy, as so many new patientsdo. Further, when another agent is added (the step most often taken next) theadd-on agent is often a diuretic.

— Anna Marie Napolitano, VP, category business leader,cardiovascular, GfK Market Measures

Recent MM&MCoverage
Product News

Pharmacology
Tekturna HCT combines the antihypertensive drugs aliskiren,a direct renin inhibitor, and the thiazide diuretic, HCTZ. Aliskiren decreasesplasma renin activity and inhibits the conversion of angiotensinogen to angiotensin I.Thiazide diuretics reduce electrolyte resorption in the renal tubules,resulting in increased diuresis along with electrolyte loss, notably potassium.Drugs that inhibit the renin-angiotensin system tend to blunt thepotassium-losing effects of the thiazides.

Clinical Trials
An 8-week, placebo-controlled study involving >2700patients with mild to moderate hypertension was conducted to evaluate thesafety and efficacy of Tekturna HCT. Various dosage combinations of aliskirenand HCTZ were given once daily to patients in this parallel-group study. Thecombination of aliskiren and HCTZ resulted in additive decreases in bloodpressure (BP) at trough compared to placebo. These reductions were greater thanthose attained with monotherapy.

One trial investigated the addition of 300 mg aliskiren in obesehypertensive patients who did not respond adequately to HCTZ 25 mg, and showeddecreases of systolic and diastolic BP of approximately 7/4 mmHg.

Additive effects of Tekturna HCT with maximal doses of ACEIs andß-blockers have not been demonstrated.

Adverse Reactions
Dizziness, diarrhea, cough, asthenia, arthralgia, elevatedBUN/creatinine, ALT, uric acid; rare: angioedema (discontinue if occurs).

Adults
Not for initial therapy. May substitute for previouslytitrated components, or switch to Tekturna HCT if inadequate response to eithertherapy alone, or if hypokalemia occurs with HCTZ monotherapy, or ifdose-limiting effects occur with either component as monotherapy. Takeconsistently with regard to meals (absorption reduced by high-fat meals).=18yrs: One tablet once daily. May titrate up if BP uncontrolled after 2–4weeks; max dose aliskiren 300mg/HCTZ 25mg.

Children
<18yrs: not recommended.

Contraindications
Anuria. Sulfonamide allergy.

Precautions
Severe renal impairment (CrCl<30mL/min): not recommended.Severe renal disease. Correct salt/volume depletion before starting, or monitorclosely. Hepatic dysfunction. Asthma. SLE. Monitor electrolytes. Pregnancy(Cat.D). Nursing mothers: not recommended.

Interactions
Lithium toxicity (avoid). Potentiates antihypertensives,possibly non-depolarizing muscle relaxants. Potentiated by ketoconazole,atorvastatin. Antagonized by irbesartan, NSAIDs. May antagonize furosemide.ACTH, corticosteroids increase hypokalemia risk. Adjust anti-diabetic drugs.Orthostatic hypotension potentiated by alcohol, CNS depressants.