Fight Against Heroin Addiction

by Food and Drug Administration (FDA)

A new approach to bringing drugs to market won high marks last year when the Food and Drug Administration approved levo-alpha- acetyl-methadol (Orlaam, also known as LAAM) in record time. LAAM is only the second synthetic narcotic medication approved to treat heroin and other opioid addiction through outpatient narcotic maintenance treatment programs. The other medication is methadone, approved almost 25 years ago.

Chronic and relapsing, heroin addiction controls its victims. It wastes lives and addicts newborns along with their mothers. It spreads infection with HIV, the virus that causes AIDS, and other infectious diseases through the sharing of dirty needles. It is connected with violent crime and casts a heavy economic burden upon society.

More than 586,000 Americans use heroin at least weekly, the Office of National Drug Control Policy reports.

LAAM was approved July 20, 1993, only 18 days after FDA received the new drug application.

The "new approach" that made this speedy approval possible involved cooperation among FDA drug review and compliance staffs, a new division of the National Institutes of Health's National Institute on Drug Abuse (NIDA), the Drug Enforcement Administration, and industry — in this case, Biometric Research Institute Inc., of Arlington, Va.

The cooperative clinical tests underpinning the approval took just 18 months from protocol development to patient enrollment, completion of the first phase of the study, and report to the agency.

NIDA's Medications Development Division (MDD) was established in 1990 to encourage development of anti-addiction medications. Although LAAM had been studied for many years, it was sitting on a "back burner" at NIDA.

About the same time MDD was created, FDA set up its Pilot Drug Evaluation Staff to streamline drug approval. The agency assigned review of anti-addiction medications to the new staff, and hired experts in drug abuse issues, including senior scientist Michael Klein, Ph.D.

"In 1990, we advised NIDA," Klein says, "to reassemble the data on LAAM submitted in the 1980s in two rejected new drug applications, and give them back to us as an investigational new drug application. The IND gave us a way to get involved in development from step 1, and make recommendations for the eventual submission of the NDA."

Klein and others reviewed the IND and parceled out certain older studies for review by FDA's Drug Abuse Advisory Committee.

"We also wanted studies of the new population of patients," Klein says. "Many people abusing heroin today also use other drugs, such as crack cocaine, which wasn't around in the early 1980s."

MDD conferred with FDA to develop directions for using LAAM. Researchers were to follow the directions, spot problems, and try to correct them. To eliminate bias, FDA specified using only clinics that had never studied LAAM.

MDD contracted for the FDA-guided trials with 26 Department of Veterans Affairs (VA) medical centers and university clinics. According to MDD health scientist administrator Paul Coulis, Ph.D., "We worked with FDA all along, sharing our findings as they developed."

Klein says, "We got a very nice picture of the adequacy of the labeling and potential problems today, which we could couple with the old studies, some of which did show efficacy."

Maintenance Medications, Close Up

Methadone and LAAM are oral narcotics that work in the body much like morphine does. When taken for short periods by non- addicts, they kill pain, sedate the central nervous system, and relax smooth muscle tissues.

Both medications can themselves produce dependence. But when taken as part of a maintenance treatment program, they do not cause euphoria. They in fact block the "highs" of other opioid narcotics, such as heroin, and suppress the symptoms of withdrawal. These symptoms include increased blood pressure and temperature, rapid heartbeat, "goose-flesh" (piloerection), runny nose (rhinorrhea), watery eyes (lacrimation), tremors, insomnia, vomiting, abdominal cramps, restlessness, weakness, headache, hot or cold flashes, and drug craving. Withdrawal from methadone or LAAM causes similar symptoms, but starts more slowly, is less severe, and continues for a longer time.

LAAM's advantage is that it works for 48 to 72 hours after a dose is taken, compared to 24 hours for methadone. With fewer required visits, patients have the chance to lead a more normal existence and clinics have the option to treat more patients.

Methadone must be given every day, and take-home doses are permitted in selected cases.

LAAM is not approved for daily treatment because daily use of the usual doses will lead to serious overdose. Evaluated only as an in-clinic medication, LAAM is not allowed in take-home doses. In extreme situations, however, certain LAAM patients may be temporarily switched to methadone for a take-home dose when they know in advance they can't come to the clinic for a scheduled LAAM dose. Also, in-clinic dosing reduces the likelihood of patients' diverting the medication to street sales.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.