December 17, 2007
Treatment of high blood pressure.
Nebivolol 2.5mg, 5mg, 10mg; tabs.
Sudler & Hennessey (Professional)
Does the world need another beta blocker? Forest Labs and
Mylan say their newly approved ß-blockade drug, Bystolic, is different. According
to Charles Triano, Forest VP, investor relations, setting the new drug apart
from traditional beta blockers are its greater tolerability, vasodilating
qualities and efficacy in a broader group of patients, including blacks. Those
insights are likely to feature in promotions. Don't look for Forest
to advertise on TV or use other common DTC tactics, though. “The typical Forest model is a lot of physician education right to the
prescriber level,” Triano said. That means some patient outreach via the
Internet, but mostly the firm will rely on physician education from its roughly
2,000 reps detailing Bystolic, as well speaker programs. Another method
preferred by Forest is journal advertising, in
this case through multi-page buys in the minimass publications. The company
will also work with managed care organizations to get the drug covered.
Beta blockers US sales ($000s) last 5 years
|Source: IMS Health, Jan. 2008
Top 5 beta blockers
||Jan.-June '07 US sales ($000s)
||% sales growth over Jan.-June ‘06
|INDERAL LA (Wyeth)
|Source: IMS Health, Jan. 2008
Nebivolol (Bystolic) is a new beta blocker expected to
launch early in 2008. Forest, which licensed
the product from Mylan in 2006, plans to introduce this new hypertension
treatment in a market already crowded with generic options, including generic
beta blockers. Forest believes that despite
the cost pressures, Bystolic's low sedation level will be the competitive advantage
that drives its use. According to GfK Market Measures 2007 Treatment of
Hypertension Physician research, of the 20% of beta blocker users who have a
problem with side effects, fatigue is the number-one complaint. Nebivolol is
currently in Phase III research as well for treatment of heart failure.
—Anna Marie Napolitano, VP, category business leader,
cardiovascular, GfK Market Measures, Dec. 2007
Also in the Pipeline
(according to Adis R&D Insight)
Drug: TAK 491
Active Ingredient: Azilsartan
Manufacturer: Addrenex Pharmaceuticals
Active Ingredient: Clonidine
Drug: HMR 4005
Manufacturer: Abbott GmbH & Co. KG
Active Ingredient: Darusentan
Active Ingredient: Clevidipine
Manufacturer: Eli Lilly
Active Ingredient: Moxonidine
Drug: Altace ATC, Triatec HCT
Active Ingredient: Hydrochlorothiazide/ramipril
Manufacturer: Encysive Pharmaceuticals
Active Ingredient: Sitaxsentan
Source: Wolters Kluwer Health
Recent MM&M News
Journal Ad Review
warns Bayer on YAZ TV ads
Nebivolol is a once-daily ß-adrenergic blocking agent that, at doses up to 10mg, is primarily ß1-selective. In poor metabolizers (those with reduced activity of CYP2D6) and at higher doses, however, it may inhibit ß2 adrenergic receptors as well. ß2
blockade may lead to bronchoconstrictive effects. Nebivolol does not
have intrinsic sympathomimetic effects or membrane stabilizing activity
at therapeutic doses. It has several active metabolites which are the
product of glucuronidation and hydroxylation by the oxidative enzyme
Possible factors that may contribute to nebivolol
antihypertensive activity include decreased heart rate and myocardial
contractility, reduced sympathetic tone, suppression of renin activity,
and vasodilation and reduced peripheral vascular resistance.
Three double-blind, placebo-controlled, 12-week studies were conducted
to demonstrate the effectiveness of nebivolol as monotherapy in the
treatment of hypertension. Two of these trials studied 1716 patients in
the general hypertensive population (26% non-Caucasian) and a third
studied 300 Black (African-American) patients. Another study, which
enrolled 669 patients, evaluated the effect of adding nebivolol to a
background anti-hypertensive regimen of up to two other agents,
including ACEIs, ARBs, and thiazide diuretics. In each study, nebivolol
was shown to be effective in lowering both systolic and diastolic BP.
Effectiveness was established in Black patients, but as monotherapy the
magnitude of effect was somewhat less than in Caucasians. The
BP-lowering effect was seen at 2 weeks after starting therapy and was
maintained over the 24-hour dosing interval.
Headache, fatigue, dizziness, GI upset.
=18yrs: initially 5mg once daily. Individualize; may increase at 2-week
intervals; max 40mg/day. Severe renal or moderate hepatic impairment:
initially 2.5mg once daily.
<18yrs: not recommended.
Severe hepatic impairment (Child-Pugh >B). Severe bradycardia. 2nd-
or 3rd degree AV block. Cardiogenic shock. Overt heart failure. Sick
sinus syndrome (unless paced).
CHF. Angina. Recent MI. Bronchospastic disease. Diabetes.
Hyperthyroidism. Severe renal impairment. Moderate hepatic impairment.
Avoid abrupt cessation (taper over 1–2 weeks). Surgery. Peripheral
vascular disease. Pheochromocytoma. Pregnancy (Cat.C). Nursing mothers:
Caution with phenylalkylamine and benzothiazepine calcium channel
blockers (eg, verapamil, diltiazem), antiarrhythmics (eg disopyramide),
digoxin, reserpine, guanethidine; monitor. May be potentiated by CYP2D6
inhibitors (eg, quinidine, propafenone, paroxetine, fluoxetine); may
need to reduce dose. If on both nebivolol and clonidine, discontinue
nebivolol before tapering clonidine. May block epinephrine.