Ms. Domenici and Dr. Patel are both
pharmacists at Brigham and
Women's Hospital, Boston, Mass.
Exforge (amlodipine/valsartan tablets)
received full FDA approval on June 21,
2007, for the treatment of high blood
pressure.1 A tentative approval had
been granted to Novartis on December
22, 2006, pending the patent expiration
of amlodipine, which is found in Pfizer's
Norvasc.2 Valsartan is marketed under
the name Diovan by Novartis.
Exforge is a novel single-entity tablet
combining amlodipine, a dihydropyridine
calcium channel blocker, and valsartan,
an angiotensin receptor blocker.
Exforge approval was based on several
placebo- and active-controlled trials.
Amlodipine blocks the transmembrane
influx of calcium ions into the
vascular smooth and cardiac muscles,
causing a reduction in peripheral vascular
resistance and blood pressure.3
Amlodipine goes through hepatic
metabolism to inactive metabolites.
Elimination is biphasic, with a terminal
half-life of 30 to 50 hours. The dose
should be adjusted in patients with
Angiotensin II binds to angiotensin
type 1 (AT1) receptors, causing vasoconstriction,
and aldosterone production—all of
which cause an increase in blood pressure.
Valsartan has a high affinity for
AT1 receptors. Blockade of these receptors
causes a decrease in blood pressure.
Peak plasma concentrations after
oral administration are reached within
2 to 4 hours.
Exposure of valsartan is increased by
2-fold in patients with mild-to-moderate
liver disease.3 A dosage adjustment
is not recommended, but precautions
should be exercised in patients with
The results following oral administration
of Exforge, in terms of the rate and
extent of absorption, are similar to
those following the administration of
the 2 components as individual tablets.3
A phase 3, double-blind, placebocontrolled
trial enrolled 1250 patients
diagnosed with mild-to-moderate hypertension,
which was defined as diastolic
blood pressure of ≥95 and <110
mm Hg.4 Average blood pressure was
156.7/99.1 mm Hg in patients in all
treatment assignments. Patients were
randomized to receive once-daily treatment
for 8 weeks with 1 of the following:
- Amlodipine 10 mg
- Valsartan 160 mg or 320 mg
- Exforge 10 mg/160 mg
- Exforge 10 mg/320 mg
At week 8, the 10-mg/320-mg dosage
decreased diastolic blood pressure
from baseline by 18.6 mm Hg and the
10-mg/160-mg dosage by 17.6 mm Hg.
Both Exforge doses reduced diastolic
blood pressure to a greater extent than
the monotherapy doses. Median systolic
blood pressure reductions were
consistent from baseline in both
The Exforge 10-mg/320-mg arm
demonstrated the greatest percentage
(73%) of patients achieving a blood
pressure of <140/90 mm Hg. Although
stage 1 and 2 hypertension were not
prespecified subgroups, both Exforge
groups were superior in achieving a
blood pressure of <140/90 mm Hg (58%
and 75%, respectively) for stage 1
hypertension and 25% and 33% for
The higher Exforge dose also was
more successful in achieving the more
aggressive blood pressure goal of
<130/80 mm Hg, compared with monotherapy.4
The most common adverse events
with Exforge were nasopharyngitis,
upper respiratory tract infection, asthenia,
and fatigue. Other reported adverse
events due to the amlodipine part of
Exforge were peripheral edema and
Exforge is indicated for the treatment
of hypertension in patients who
have failed to control their blood pressure
with monotherapy with amlodipine
or valsartan, but not for initial therapy.
Exforge tablets are available in the
following combinations: 5 mg/160 mg, 5
mg/320 mg, 10 mg/160 mg, and 10
mg/320 mg. The product is not indicated
for use in pregnancy. If blood pressure
is not controlled after 3 to 4
weeks of therapy, the dose should be
- www.novartis.com/newsroom/news/index.shtml. Accessed August 15, 2007.
- www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed August 15, 2007.
- Product Information. East Hanover, NJ: Novartis; April 2007.
- Dear Healthcare Professional Letter. East Hanover, NJ: Novartis; August 8, 2007.