FDA Panel Backs Avalide as First-Line Hypertension Therapy


ROCKVILLE, MD. — A Food and Drug Administration advisory panel unanimously recommended that the combination antihypertensive product irbesartan and hydrochlorothiazide (HCTZ) be approved as a first-line treatment for hypertension.

At a meeting on April 18, the Cardiovascular and Renal Drugs Advisory Committee voted 7–0 in favor of approving the fixed-dose angiotensin receptor blocker-diuretic combination product as initial therapy.

The company has proposed that Avalide be indicated as initial treatment of severe hypertension. The panel was asked to comment on the wording of the indication statement that would be included in the label. Several were supportive of wording that Avalide can be considered as initial treatment when control of blood pressure is not likely to be achieved with one drug, or for moderate to severe hypertension.

The product, marketed as Avalide by Bristol-Myers Squibb (BMS), was approved in 1997 for treating hypertension, with a statement in its label that says the combination therapy should not be used until a patient has failed to achieve the desired effect with monotherapy.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

The combination antihypertensives that have previously been approved as first-line treatments are Capozide (captopril and HCTZ), Ziac (bisoprolol/HCTZ), and Hyzaar (losartan/HCTZ).

At the meeting on Avalide, BMS provided the results of two studies. The first, a pivotal trial of 695 patients (mean age was 52) with severe hypertension (an untreated diastolic blood pressure of at least 110 mm Hg or on monotherapy with a diastolic blood pressure of at least 100 mm Hg), compared Avalide with irbesartan monotherapy as initial therapy. The second, a supportive trial, compared Avalide with irbesartan and HCTZ monotherapies in patients with moderate hypertension. The studies used forced titration to 300 mg/25 mg of Avalide, 300 mg of irbesartan, or 25 mg of HCTZ.

In the pivotal trial, 47% of those on Avalide had achieved a diastolic blood pressure below 90 mm Hg at 5 weeks, the primary end point, compared with 33% of those on irbesartan monotherapy, a highly significant difference.

Among black subjects (about 14% of the subjects), 40% of those on Avalide had achieved a diastolic blood pressure below 90 mm Hg at 5 weeks, compared with nearly 15% of those on irbesartan. In diabetic subjects, 33% had achieved blood pressure goal below 140/90 mm Hg, compared with 23% of those on irbesartan at 5 weeks.

Overall, Avalide was safe and well tolerated, and was comparable to irbesartan monotherapy, with no increase in dizziness or syncope and no serious adverse events related to treatment. No deaths were reported, according to BMS.

About 4% of patients in each group experienced dizziness, and headache was reported in 4% of those on Avalide, and 6% of those on irbesartan. Hypotension was reported in 0.6% of those on Avalide, and none of those on monotherapy.

About 2% in each group discontinued treatment for an adverse event. Among the 92 patients 65 and older, Avalide was well tolerated, there were no cases of hypotension or syncope, and dizziness was no more common than in younger patients.

In the supportive study of about 500 patients with moderate hypertension, Avalide was more effective in reducing blood pressure than either irbesartan or HCTZ alone, had a comparable safety profile, and was well tolerated in the elderly, according to BMS.

Several members of the advisory panel said that the company should get more data on the combination as first line treatment in elderly patients and in patients with renal dysfunction.

Approval as a first-line treatment would not affect the patent for Avalide, which expires in 2012, a BMS spokesperson said.

Recommended Reading

Aliskiren's Benefits May Go Beyond BP Control
MDedge Cardiology
Big Gains in BP Control Seen Since JNC-7
MDedge Cardiology
Chinese Study Finds No Blood Pressure J-Curve
MDedge Cardiology
Biofeedback Cuts BP in Type 2 Diabetes
MDedge Cardiology
Hypertension in Pregnancy Tied to Late CV Events
MDedge Cardiology
Early BP Screening in Offspring of Stroke Patients Warranted
MDedge Cardiology
Sleep Apnea and HT Tied in Kidney Disease
MDedge Cardiology
Weight Loss in Prehypertension Cuts Risks, Helps Avoid Medication
MDedge Cardiology
Aldosterone Tied to Metabolic Syndrome in Hypertensive Blacks
MDedge Cardiology
Pediatric Hypertension Is Linked To Sleep-Disordered Breathing
MDedge Cardiology