Rockville, MD - The US FDA has approved the first combination of an angiotensin receptor blocker (ARB)—valsartan—with a calcium-channel blocker (CCB)—amlodipine—for the initial treatment of hypertension. The product, known as Exforge, was given the additional indication along with another combination containing valsartan and hydrochlorothiazide, Diovan HCT [1]. Both are marketed by Novartis.

The products were already available for the second-line treatment of high blood pressure—Exforge having first been approved just last year. Hypertension expert Dr Franz Messerli (St Luke's Roosevelt Hospital, New York) told heartwire that the new indication for Exforge "is by far the more important of the two, because valsartan and amlodipine are the most commonly prescribed ARB/CCB combination, and this is the first time such a combination has been approved for initial therapy."

Messerli welcomes the approval—"I think this is a major progress"—but cautions that "patient selection is crucial when it comes to using fixed-dose combinations, because they are not for every patient. A decade ago the pharmaceutical companies were taking out full-page ads stating that 80% of patients can be controlled on drug X monotherapy, and now they are saying that more than 80% of patients need combination therapy. I suspect the truth is somewhere in between, with around 50% to 65% of patients needing combinations."

A decade ago the pharmaceutical companies were taking out full-page ads stating that 80% of patients can be controlled on . . . monotherapy, and now they are saying that more than 80% of patients need combination therapy.

Messerli says the FDA has "been fairly trigger-happy to approve diuretic-based combinations" but slightly more reluctant to grant approvals of other fixed-dose combinations, particularly for initial therapy, for the simple reason that it fears that some patients will be exposed unnecessarily to combination treatment.

But he believes that physicians have been erring on the side of caution in this regard, "as they are a bit reluctant to be too aggressive in lowering blood pressure too fast." However, "the ACCOMPLISH study really has put fixed combinations on the map, and therefore physicians have been using them, which is not surprising," and some doctors have been using Exforge off-label for the initial treatment of hypertension, "so in some ways the FDA is belatedly blessing what many physicians have been doing for quite some time."

Another expert, Dr Elizabeth Ofili (Morehouse School of Medicine, Atlanta, GA), agrees, adding that "it is important to get the first-line approval for a number of reasons, one of which is managed care. The FDA is moving toward this area and recognizing that high blood pressure is a complex process." Messerli says such approvals also allow the companies to market their products as first-line therapy, something they have previously been unable to do.

"There are two main advantages of fixed-dose combinations for the patient," he says. "First, the pill burden is reduced, and second, the patient only has one copayment instead of two."

Both Messerli and Ofili said that there would not be too much competition from generics for the new Exforge product or for other similar combinations at the present time. Although amlodipine has recently become available generically in the US, it is not that cheap, they point out.

"Once amlodipine becomes a Wal-Mart $4 drug, it's obvious that cost will become an issue," says Messerli. None of the ARBs are yet available generically in the US, he adds, although losartan will be available next year.