New FDA Approvals

The following drugs have received final approval from the Food and Drug Administration (FDA):

Dutasteride (Avodart) by GlaxoSmithKline. The FDA has approved a supplemental new drug application for dutasteride (Avodart) for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve urinary symptoms, reduce risk of acute urinary retention, and reduce the risk of the need for BPH-related surgery.

Dutasteride, a second-generation 5 alpha-reductase inhibitor, inhibits both the type 1 and type 2 enzymes responsible for the conversion of testosterone to DHT (dihydrotestosterone). Dutasteride’s dual inhibition decreases levels of DHT by 90% at two weeks and 93% at two years. Although improvement in urinary symptoms was seen in some patients by three months, a therapeutic trial of at least six months is usually necessary to assess whether a beneficial response in symptom relief is achieved with dutasteride.

Clinical trials of dutasteride showed that it was generally well-tolerated. Most side effects were mild or moderate and generally went away while on treatment in both the dutasteride and placebo groups.

Buprenorphine hydrochloride (Subutex) and buprenorphine hydrochloride and naloxone hydrochloride (Suboxone tablets) by Reckitt Benckiser Pharmaceuticals. The FDA has approved buprenorphine hydrochloride (Subutex) and buprenorphine hydrochloride and naloxone hydrochloride (Suboxone tablets) for the treatment of opiate dependence.

These products represent two new formulations of buprenorphine. Buprenorphine hydrochloride is intended for use at the beginning of treatment for drug abuse. Buprenorphine hydrochloride and naloxone hydrochloride is intended to be the formulation used in maintenance treatment of opiate addiction. Both drugs are supplied in 2 mg and 8 mg tablets, which are placed under the tongue and must be allowed to dissolve.

Based on the potential for abuse of the drugs, the FDA and its parent Department of Health and Human Services recommended that the Drug Enforcement Administration (DEA) place buprenorphine in Schedule III under the Controlled Substances Act. Buprenorphine hydrochloride and buprenorphine hydrochloride and naloxone hydrochloride are the first narcotic drugs available for the treatment of opiate dependence that can be prescribed in an office setting under the Drug Addiction Treatment Act (DATA) of 2000.

The provisions of the DATA include limits on the number of patients individual physicians are allowed to treat and special DEA registration for the use of this drug, thus providing additional safeguards as this drug enters the office-based treatment setting.

Peginterferon alfa-2a (Pegasys) by Hoffmann-La Roche. The FDA has approved Peginterferon alfa-2a (Pegasys) for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated cirrhosis.

Peginterferon alfa-2a is a pegylated interferon that remains active in the bloodstream longer and at a more constant level than interferon alpha. Clinical trials of peginterferon alfa-2a have shown that patients can determine at 12 weeks if they are unlikely to attain a sustained virological response with peginterferon alfa-2a.

Alpha interferons, including peginterferon alfa-2a, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations.

Roche will be providing physicians with samples of peginterferon alfa-2a for the first 12 weeks of therapy. These samples will be provided at the request of a physician for the first 15,000 patients who are started on peginterferon alfa-2a therapy prior to Dec. 31, 2002. Peginterferon alfa-2a is dosed at 180 µg as a subcutaneous injection once a week for a recommended duration of 48 weeks.

Ezetimibe (Zetia) by Merck/Schering-Plough Pharmaceuticals. The FDA has approved ezetimibe (Zetia), the first in a new class of cholesterol-lowering agents that inhibits the intestinal absorption of cholesterol. The once-daily tablet of ezetimibe 10 mg was approved for use either by itself or together with statins in patients with high cholesterol to reduce LDL cholesterol and total cholesterol. The FDA also approved ezetimibe for use in two rare genetic disorders: homozygous familial hypercholesterolemia and homozygous sitosterolemia.

Ezetimibe’s mechanism of action makes it complementary to statins, which work in the liver. A multicenter study showed that adding ezetimibe to ongoing statin treatment provided a 25% additional reduction in LDL cholesterol vs. 4% with the addition of placebo.

In clinical trials, ezetimibe was generally well-tolerated, with an overall side effect profile similar to placebo. When ezetimibe is used with a statin, liver function tests should be performed at the start of therapy and after that in accordance with the label for that statin. Liver function tests are not required when ezetimibe is used alone. Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic insufficiency, ezetimibe is not recommended in these patients.

Rosiglitazone maleate and metformin hydrochloride (Avandamet) by GlaxoSmithKline. The FDA has approved rosiglitazone maleate and metformin hydrochloride (Avandamet) for the treatment of type 2 diabetes. Rosiglitazone maleate and metformin hydrochloride combines two leading diabetes medications in one pill.

As an adjunct to diet and exercise, rosiglitazone maleate and metformin hydrochloride is indicated to improve blood sugar control in people with type 2 diabetes who are already treated with rosiglitazone and metformin as separate tablets, or who are not adequately controlled on metformin alone. It is available in three tablet strengths of rosiglitazone/metformin, respectively: 1 mg/500 mg, 2 mg/500 mg, and 4 mg/500 mg.

Rosiglitazone maleate and metformin hydrochloride should not be used in patients with renal disease or dysfunction or with congestive heart failure requiring medication. Before using the drug, patients over the age of 80 should have their renal function tested to ensure that their kidney function is adequate.

Rosiglitazone maleate and metformin hydrochloride is also not recommended for people with liver disease. Patients should inform their doctor if they drink alcohol excessively.

Glipizide and metformin hydrochloride tablets (Metaglip) by Bristol-Myers Squibb Co. The FDA has approved the marketing of glipizide and metformin hydrochloride in a single tablet (Metaglip) for use, along with diet and exercise, as initial drug therapy for people with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone. Glipizide and metformin hydrochloride tablets was also approved as second-line therapy for patients with type 2 diabetes who are currently taking either metformin or a sulfonylurea with a regimen of diet and exercise, but whose blood sugar levels are inadequately controlled.

Glipizide and metformin hydrochloride tablets will be available in three dosage strengths, including 2.5 mg of glipizide and 250 mg of metformin hydrochloride, 2.5 mg of glipizide and 500 mg of metformin hydrochloride, and 5 mg of glipizide and 500 mg of metformin hydrochloride.

Patients should not take these products if they have kidney problems, are 80 or older (unless their kidneys are tested), are taking medication for heart failure, are seriously dehydrated, have a serious infection, or have or have had liver disease.

New indication for repaglinide (Prandin) by Novo Nordisk. The FDA has approved a new indication for use of the oral antidiabetic drug repaglinide (Prandin): as combination therapy with rosiglitazone or pioglitazone for the treatment of type 2 diabetes. Prandin, an insulin secretagogue, was previously approved for use as monotherapy or in combination with metformin.