DAVE SIDAWAY, GAZETTE / Charles Hammock's widow, Peggy-Ann, wants Zyban off the market.

In the database of the world's largest drug company, the premature death of Charles Hammock at age 48 is listed as Adverse Event No. CD/00/4960.

A Bombardier aircraft upholsterer who lived in Lachine, Hammock died suddenly the morning of Aug. 17, 1999, 10 days after starting treatment with Zyban, the anti-smoking pill.

His widow and five children suspect the drug killed him.

His family doctor reported a possible connection. But a Quebec coroner last March concluded Hammock had died of natural causes: fatal arrhythmia.

What led to those abnormal heart rhythms, which were serious enough to cause cardiac arrest, severe enough to cause Hammock to collapse on the job and die?

Was it the drug? Was it because Hammock, a pack-a-day Belvedere smoker since his teens, already ran a high risk of heart failure? Or was it a symptom of his withdrawing from a lifelong addiction to nicotine?

On those kinds of questions hinges the worldwide debate over the safety of Zyban, a top-selling medication that was launched in 1997 and is used by one million Canadians and 14 million other people worldwide.

The drug is being investigated as the possible cause of at least four other deaths in Canada, including that of 26-year-old Montrealer David Landry in February, as well as of 18 deaths in Britain and one in Australia.

GlaxoSmithKline, the British-based pharmaceutical giant that makes Zyban, denies any proven link so far between its drug and the fatalities. So do investigators at Health Canada and other countries' health authorities.

What makes many of the cases disturbing is how relatively healthy - for smokers - some of the patients like Hammock were before they started taking Zyban, and how sudden and unexpected their deaths were.

Zyban's active ingredient, bupropion hydrochloride, a kind of anti-depressant, also is marketed to psychiatric patients (as well as some smokers) under the brand name Wellbutrin.

A stimulant, it works by changing the balance of chemicals in the brain to reduce a person's craving for nicotine. A typical treatment lasts three months, with the patient quitting smoking after the first week.

Studies suggest one in three patients on Zyban remains off the weed even a year later. Hammock didn't get that far.

"Charlie quit smoking, but unfortunately he had to quit breathing to do it," his widow, Peggy-Ann Scott-Hammock, quipped bitterly in an interview this week, lamenting the sudden end of a marriage that lasted 31 years.

"It was my worst nightmare. You say goodbye to your husband in the morning on his way to work, and he doesn't come home."

A trim 159 pounds, Hammock had an otherwise clean bill of health before he started taking Zyban, his medical chart shows: normal blood pressure, low cholesterol levels, no history of heart or lung problems.

After a checkup on July 28, 1999, and a series of routine lab tests, his family doctor pronounced him fit enough "to live to 100," Scott-Hammock told The Gazette.

Hammock had been encouraged to quit smoking with Zyban after hearing how well it had helped a co-worker at Bombardier break her habit. And he'd seen ads for the product on U.S. cable TV.

Ten days after his physical, he got his prescription filled. But after a few days of popping the little purple Zyban pills, first once, then twice every 24 hours, something went wrong.

"He started telling me how peculiar he felt," said Scott-Hammock, who works as the daycare supervisor at Meadowbrook elementary school in Lachine.

"As a family, we noticed he was majorly agitated. I kept saying to him, 'Charlie, maybe you shouldn't be taking this Zyban.' But he thought the side-effects would wear off after a few days, so he stayed on it."

The night before he died, there was a major blowup at the family supper table. Hammock was testy, irritable, far more than he'd ever been in previous attempts to quit smoking. "I said, 'Calm down, you're going to have a stroke,' " Scott-Hammock recounted.

Like other anti-depressant drugs, Zyban carries a significant risk of seizures: one in 1,000 people will have fits or go into convulsions as result of taking it.

According to Glaxo's lengthy monograph for Zyban, 2 per cent of patients will also experience some heart palpitations while on it. But the jury is out on whether those palpitations can be deadly.

The monograph only warns doctors to be careful prescribing the drug to patients who've had a recent heart attack and other cardiac problems, saying studies have yet to prove its safety for those people.

Early on the morning of his death, around 8:30 a.m., Hammock phoned his wife from work to say he'd had a bad dizzy spell. He also told his supervisor he had a headache, the coroner's report shows.

Less than two hours later, he collapsed in Dorval. At 10:20 his supervisor found him unconscious, lying on the floor of the Canadair Global Express jet on which he'd been working.

His heart was beating but he had no pulse and he wasn't breathing.

An Urgences-Sante technician tried to revive him with a defibrillator, but it was too late. After an ambulance ride to Sacre Coeur Hospital, Hammock was pronounced dead.

His family was left in shock, searching for answers. They called his doctor. They called Glaxo Canada's telephone helpline and talked to a company nurse. The closest they got to an explanation was two months ago, when another official called back.

"The woman told me my husband's case was now registered in an international database of adverse events to Zyban, and that the company was accumulating evidence," Scott-Hammock recalled.

"I told her that wasn't good enough. I told her, 'How many people are going to die before you pull this drug from the market? When will we as consumers know there's something wrong with this drug?' "

The Glaxo official pointed out that as a smoker Hammock had been at risk of heart disease. " 'But he didn't have heart disease, and he didn't die of it, either,' " the widow remembers responding. " 'He went from perfectly healthy to dead in 10 days. Explain that.' "

This week, Glaxo Canada's chief medical officer tried.

"It's always a difficult call" whether the death of a patient like Hammock "was due to an underlying problem or due to the drug," said Dr. Anne Phillips, an infectious-disease specialist who is the company's vice-president of research and development.

"People who smoke are at greatly increased risk: they're about five times more likely than non-smokers to have a heart attack or heart problems," she said from Glaxo Canada headquarters in Mississauga, Ont.

"So these events occurring in a patient population which is taking the medication doesn't necessarily, of course, implicate the medication as the cause."

According to Health Canada data dating back to September 1999 - the most recent it and the company say are available - there have been 407 adverse events related to Zyban and 67 related to Wellbutrin.

Of the Zyban events, 312 involved three deaths, seven non-fatal heart attacks, 64 convulsions or seizures, seven cases of hypoglycemia (low blood sugar), 163 allergic reactions, 52 psychiatric reactions (including one suicide attempt), and 16 reports of vision problems.

Health Canada's Therapeutic Products Program, which monitors drug safety, "continues to work with the manufacturer to re-evaluate and update the safety profile of Zyban," it said in a January 2000 report.

Asked about the hundreds of adverse events, Glaxo's Phillips said she wasn't surprised.

"The more people that take any product, even Aspirin, the more side-effects or adverse events are going to be reported," she said.

"When you have that number of people (more than one million Canadians on Zyban) taking anything, even taking a glass of water, some are going to report different adverse events."

What about possible effects on the heart? Shouldn't Zyban users be warned about palpitations - and stop taking the drug at the first sign of them?

"Not necessarily," Phillips said.

"I mean, you have to remember the context in which this product is being used: during withdrawal from an addicting substance (nicotine). And one of the side-effects of withdrawal is often palpitations."

Coming off a nicotine addiction is never pleasant, she added. "It tends to cause a series of physical symptoms: anxiety, palpitations, insomnia are all very common withdrawal syndromes."

Aren't the unexpected deaths of younger Zyban patients like Hammock and especially the 26-year-old Landry last month rather unusual?

Not really, Phillips said.

"We have young people who die suddenly all the time. You hear reports of kids in the gym playing basketball or whatever dropping dead. Young people do die sudden death."

Will the survivors of Zyban patients like Hammock never get a definitive answer? Will they never know for sure whether Zyban did or did not kill their loved one?

Perhaps not, Phillips said.

Just as the families of cancer victims can't know if the drugs in chemotherapy did more harm than good, those with experience with Zyban may never get the answer they're looking for.

"Cancer drugs are just as hard to decide," Phillips noted. "Are adverse events a side-effect of the medication or a progression of the malignancy? We're always faced with these difficult situations."

Scott-Hammock can't shed her suspicions, though. Zyban and Wellbutrin are a $70-million-a-year business for Glaxo in Canada.

If the products are tarnished by safety concerns, the firm stock could take a hit.

"They may be watching the value of their stock," she said.

"But it seems to me that when there are as many sudden deaths as this, Glaxo should be erring on the side of caution and pulling Zyban off the shelves."

For now, Adverse Event No. CD/00/4960 languishes in an international registry, part of a puzzle, perhaps, or simply a footnote in the controversial history of a popular drug.

"I'll be sure to put that on his tombstone," his widow said sardonically. "'Here lies my husband, part of the evidence in an international database.' I'm sure Charlie would like that."

- Jeff Heinrich can be reached at jheinrich@thegazette.southam.ca.