January 2001 Therapeutics Letter

Jan 2001                                             Bruce H. Woolley, Pharm.D., Editor                                        Vol. 8, No. 1
Kenneth J. Hunt, Associate Editor

Resources for Influenza Treatment and Prevention

As the winter season is in full force, influenza is once again becoming an important health care dilemma. The myriad of information on vaccines and treatments changes frequently and is difficult to keep track of. Though uncomplicated influenza will improve with or without treatment, the illness may cause substantial discomfort and may limit activities of daily living for days or weeks before getting better. Complications of influenza can include bacterial infections, viral pneumonia, and cardiac and other organ system abnormalities. Many other diseases, including serious infections such as rapidly progressive bacteremias, may start with symptoms that resemble influenza and may need to be considered in treatment decisions.

Many patients with uncomplicated influenza use over-the-counter medicines to help reduce their symptoms. Antiviral drugs can also help to reduce the time it takes for symptoms to improve in uncomplicated illness caused by influenza virus. Recent increases in the number and promotion of antiviral drugs for influenza have increased interest in the role of specific antiviral drugs for this condition.

Complications of influenza, and other illnesses that resemble influenza, may require additional treatment and may need urgent medical attention. It is important to inform patients that use of antiviral drugs does not eliminate the risk of complications, and some complications can be life threatening. Some strains of the influenza virus can also become resistant to specific anti-influenza antiviral drugs. Patients should be warned of the side effects associated with influenza drugs and informed about which to report.

The Food and Drug Administration's web site contains links to several sources of general information about influenza. The site concentrates on links related to influenza vaccine and antiviral drugs that have been approved in the United States for influenza. This is an excellent tool for health care providers to remain current with the ever-changing protocols of influenza treatment and prevention.

Source: http://www.fda.gov/cder/drugs/antivirals/influenza/

The Pathophysiology of 'Ecstasy'

According to national and local reports on the use of "club drugs," the compound 3,4-methylenedioxy-methamphetamine (MDMA) or ('ecstasy') has become a popular illicit hallucinogenic drug. A study published in the December 19, 2000 issue of the Annals of Internal Medicine demonstrates that moderate amounts of ecstasy have similar hemodynamic effects as dobutamine.

A multicenter team of researchers conducted a double blind, placebo-controlled study of eight healthy adults with a history of ecstasy use. Investigators separately tested the echocardio-graphic effects of ascending doses of dobutamine versus MDMA. After moderate doses (1.5 mg/kg) of MDMA, the mean heart rate increased by 28 beats per minute, and the mean systolic and diastolic blood pressures increased by 25 mm Hg and 7 mm Hg, respectively. These increases were similar to those that occurred after administration of 20 mcg/kg and 40 mcg/kg doses of dobutamine.

MDMA also raised cardiac output by 2 liters per minute, which the researchers report was similar to that produced by the 20 mcg/kg dose of Dobutamine. The major difference between the drugs was that MDMA does not have an inotropic effect, meaning there is little increase in contractility with ecstasy while dobutamine makes the heart more efficient. This effect, according to the article, probably decreases the amount of cardiac reserve, meaning that additional demands on cardiac function may not be met after use of MDMA.

The researchers noted that the cardiovascular effects of the drug may not be serious for a young healthy person, but may be quite detrimental for older people or those with any one of a number of heart diseases. In the case of emergency treatment of vascular instability, the researchers recommend the use of a beta-blocker coupled with a vasodilator like nitroglycerine or nitroprusside as emergency treatment.

Ann Intern Med 2000;133:969-973.

Major Sporting Events and Cardiovascular Mortality

In June of 1996, the day the Dutch soccer team was eliminated from the European soccer championship, there was a significant increase in mortality from myocardial infarction (MI) and stroke among Dutch men. Researchers speculated at the time that this increase was due to increased stress.

Researchers from the University Medical Center, Utrecht, the Netherlands, collected data on all-cause mortality and mortality from MI and stroke among Dutch men and women 45 years of age and older on the day of the game. They then compared these findings with mortality 5 days before and 5 days after the event, and for the same period in 1995 and 1997.
Among the men included in the study, mortality from MI and stroke increased on the day of the match (relative risk 1.51). About 14 excess cardiovascular deaths occurred that day, which is about a 50% higher than normal, according to the report in the December 23 issue of British Medical Journal. The investigators report that there was no increase in mortality among women.

The researchers reported that mental or emotional stress might not be the only triggers of cardiovascular events associated with a major sporting event. Heavy alcohol use, overeating and excessive smoking may have also play a role. The article concludes, "The role of trigger factors in cardiovascular disease illustrates that prevention of cardiovascular events goes beyond management of risk factors for atherosclerosis. Increased awareness of the impact of stressors in vulnerable subjects" is crucial for prevention of subsequent acute illness.

BMJ 2000;321:1552-1554.

Glaxo Wellcome Withdraws Lotronex From The Market

The FDA recently announced that Glaxo Wellcome of North Carolina has voluntarily withdrawn LotronexÒ (alosetron hydrochloride) tablets from the market. Lotronex was approved to treat Irritable Bowel Syndrome (IBS) in women. The FDA is advising patients taking Lotronex to contact their healthcare providers to discuss treatment alternatives.

This action follows a series of FDA analyses of the post-marketing reports of serious adverse events, which included 5 reports of death in patients taking Lotronex. The FDA has been specifically concerned about reported cases of intestinal damage resulting from reduced blood flow to the intestine (ischemic colitis) and severely obstructed or ruptured bowels (complications of severe constipation).

Upon completing its recent analyses of the 70 cases of serious post-marketing adverse events, including 44 hospitalizations and three deaths, the FDA's options included marketing withdrawal or a restricted drug distribution program. The restricted drug distribution program would provide: (1) safe use of Lotronex in appropriately informed patients, (2) continued access to Lotronex by severely debilitated IBS patients under closely monitored conditions, and (3) continued clinical research into the benefits, risks, and safe and appropriate use of Lotronex. The FDA recognizes that the other available treatments for IBS may offer inadequate relief from a condition that can be severely incapacitating for some patients.

Source: http://www.fda.gov/cder/drug/infopage/lotronex/lotronex.htm

Antidepressant Therapy Improves Cognitive Impairment in Elderly

Depression is one of the most common illnesses in the elderly. Some report that more than 50% of elderly Americans are depressed, and many of these cases are undiagnosed. A recent report in the December issue of the American Journal of Psychiatry states that elderly depressed patients with cognitive impairment show improvement in cognitive function following antidepressant treatment.

Researchers at the University of Pittsburgh Medical Center compared the cognitive functioning of 45 non-demented, elderly patients with major depression to that of 20 elderly controls. All of the depressed patients, who had an average age of 73 years, had responded to a trial of nortriptyline or paroxetine for 12 weeks.

Analysis of pre- and post-treatment Mattis Dementia Rating Scale scores indicated that successful depression treatment led to significantly improved cognitive functioning among elderly depressed patients with baseline cognitive impairment. These improvements were due to gains on measures of initiation/preservation and conceptualization, they add. The authors note that despite the improvement following treatment, the overall level of cognitive functioning in patients with cognitive impairment at baseline remained slightly impaired but did show significant improvement. The post-treatment performance of the 10 patients in this group remained well below that of the 35 patients with no baseline cognitive impairment, especially initiation/perseveration and memory scores.

The research group concluded that elderly depressed patients with cognitive impairment are probably at high risk of developing progressive dementia.

Am J Psychiatry 2000;157:1949-1954.

FDA Drug Approvals

New Treatment for Patients With APL The FDA recently approved Trixenox (Arsenic Trioxide/Cell Therapeutics) for the induction of remission and consolidation in patients with acute promyelocytic leukemia (APL). The injectable medication is designed for patients who have relapsed from retinoid and anthracycline chemotherapy. The patients are generally characterized by the presence of the (15;17) chromosome translocation.

Visicol Approved for Colonoscopy Preparation Visicolis a tablet sodium phosphate preparation produced by Inkine Pharmaceutical Company. It has been approved by the FDA for cleansing of the bowel as a preparation for colonoscopy, in adults 18 years of age and older.

Drug for Infertile Women Debuts Ovidrelis an injectable recombinant human chorionic gonadotropin preparation produced by Serono Laboratories, Inc. It is approved for the induction of final follicular maturation and early luteinization in infertile women who have undergone pituitary desensitization. The drug is reserved for women who have been appropriately pretreated with follicle stimulating hormones. It is also indicated for the induction of ovulation and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not due to primary ovarian failure.

New Treatment for HIV-1 Kaletra, a new lopinavir solution produced by Abbott Laboratories is indicated for the treatment of HIV-1 infection in adults and pediatric patients age six months and older.

Hypertension Tablet Approved Atacand tablets were recently approved for the treatment of hypertension.

Source: U.S. Food and Drug Administration http://www.fda.gov/cder/

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