2001 Therapeutics Letter

May / June 2001                       Bruce H. Woolley, Pharm.D., Editor                 Vol. 8, No. 5
Kenneth J. Hunt, Associate Editor

Diagnosis and Treatment of Meningitis

Meningococcal disease recently reached a 50-year high in Great Britain, resulting in a record number of lawsuits against physicians for misdiagnosing the condition. In response to this, the Meningitis Research Foundation recently issued new guidelines for general physicians in diagnosing and treating meningitis and septicemia.

The booklet produced by the Foundation focuses on diagnosing meningococcal septicemia in early stages, a task that has been known to be deceptive. In fact, the diagnosis has been missed by general physicians and emergency clinicians for some time. Emphasis is placed on key clinical tests to identify patients and provide information on appropriate treatment.

Denise Vaughan, chief executive of the foundation, said, "Meningococcal disease develops so quickly that a child could be fighting for life within hours of the onset of symptoms. This is why prompt diagnosis and effective treatment are so crucial." A recent campaign devoted to vaccination against group C meningococcus has been a resounding success, but the vaccine does not protect against the group B form of the disease. In 1999 there were about 3,500 reported cases of meningococcal meningitis and septicemia in Great Britain.

Reuters Medical News;

Labeling Changes For the Addiction Drug Orlaam

After reports about serious cardiac adverse events associated with levomethadyl acetate (Orlaamâ /Roxane), a drug for opiate addiction treatment, the FDA is intensifying warnings to physicians and patients using the drug. The FDA recently changed the Orlaam labeling to increase the strength of the warnings and to highlight these warnings in a black box, the most prominent warning that can be placed on prescription drugs.

In addition to labeling changes, the indications for Orlaam will be revised to indicate that the drug is not to be used as first line therapy. The drug should be reserved for use in treatment of opiate-addicted patients who fail to show an acceptable response to other adequate treatments for addiction. As of March 30, 2001, 10 cases of serious arrhythmias have been submitted to FDA through their MedWatch safety surveillance program. An estimated 33,000 patients have been treated with Orlaam to date.

Approved in 1993, Orlaam can be given less often than methadone, which means that patients visit the clinic less frequently and do not need to bring medication home. When the drug was approved, there were suspicions that it may prolong cardiac conduction, and as a result, the labeling included precautions about cardiac adverse events. Since then, the FDA has received small but increasing numbers of adverse event reports.

Orlaam is contraindicated in patients with known or suspected arrhythmias and any drug known to have the potential to cause abnormal heart rhythm should not be used together with Orlaam. Patient taking Orlaam should seek medical attention if they experience palpitations, dizziness, light-headedness, or seizures.

More information about ORLAAM and labeling changes, is available from Roxane Laboratories Technical Product Information at 1-800-962-8364. Cases of adverse events may be reported to 1-800-FDA-0178, or on the internet at

Insulin and Nocturnal Hypoglycemia in Diabetics

Newly approved and long-acting insulin glargine (Lantus®/Aventis) has been demonstrated as less likely to cause nocturnal hypoglycemia than NPH insulin. It is also associated with less weight gain than NPH according to findings from a multicenter study involving patients with type 2 diabetes.

The Dallas Diabetes and Endocrine Center and associates evaluated outcomes in patients who had been using insulin for at least 3 months. For the 28-week trial, 259 subjects were randomly assigned to treatment with insulin glargine at bedtime and 259 were assigned to NPH insulin at bedtime or in the morning and at bedtime. Premeal regular insulin was continued on the same basis as before the trial. Results of the trial were reported in the April issue of Diabetes Care.

A 25% reduction in nocturnal hypoglycemia was achieved in the insulin glargine-treated subjects compared with those given NPH. One insulin glargine patient experienced severe hypoglycemia compared with six NPH patients. Those treated with insulin glargine also gained significantly less weight, 0.4 kg, versus 1.4 kg in the NPH group.

According to the researchers, the lower risk of nocturnal hypoglycemia reflects the smooth, peakless activity profile of insulin glargine compared with the peak of NPH, which can result in maximum concentrations of insulin at night when given at bedtime. They suggest that the difference in weight gain may be due to supplemental caloric intake required for hypoglycemia in the NPH group.

Lantus was approved in April 2000 as a long-acting (basal) recombinant human insulin analog with a once-daily administration and a 24-hour glucose-lowering effect. This biosynthetic insulin, injected subcutaneously and designed to mimic NPH human insulin, was originally indicated for both adult and pediatric patients with Type 1 diabetes. It may now be used more prevalently for the treatment of adults with Type 2 diabetes who require basal insulin for the control of hyperglycemia and nocturnal hypoglycemia.

Diabetes Care 2001;24:631-636.

New Requirements Protect Children in Clinical Trials

The FDA recently issued an interim rule to provide additional safeguards for children enrolled in clinical trials of medical products the agency regulates. The new rule was required by the Children’s Health Act of 2000 that calls for specific measures to better promote the unique needs of children participating in clinical trials.

The rule is designed to help the FDA and clinical researchers to address many of the ethical issues that will accompany the expected increase in the enrollment of children in clinical trials. Recent initiatives have encouraged sponsorship of more pediatric clinical trials that can provide vital information about how therapeutic drugs and devices work specifically in children. Data from these trials may provide meaningful insight into how certain products can be formulated, administered and labeled in ways that maximize their benefit and minimize their risk to children.

Under the new ordinance, Institutional Review Boards responsible for maintaining safeguards for clinical trial subjects will now have specific standards for determining whether proposed pediatric clinical trials can be ethically conducted. Standards and procedures will be set for assuring that children have assented to participating in clinical trials, and that their parents or guardians are able to give fully informed consent to the child’s participation in a study.

Read more about this and other FDA rules at

Provider Status for Pharmacists Needed?

Two of the nation's leading pharmacy organizations recently joined forces to gain "health care provider" status for pharmacists under the Medicare program. The Pharmacist Provider Coalition, which is made up of the American Society of Health-System Pharmacists (ASHP) and the American College of Clinical Pharmacy (ACCP), is working to educate members of Congress and the public about the role pharmacists play in the safe and effective use of medications.

Under the current Medicare system, pharmacists are only paid for providing patient care services that are "incident to" that of a physician's service. This means that pharmacists working in outpatient settings can only bill for a small number of services, limiting patient access to those services. In addition, care for high-risk patients is not covered. The hazards of adverse effects from taking multiple medications affect all age groups. According to a recent ASHP survey, just over half of all Americans take at least two medications each day and nearly one-third take 4 or more medications each day. For the Medicare population, medication use is even higher.

Studies have shown that when a pharmacist is directly involved in patient care, patients have fewer adverse drug reactions, experience improved outcomes, and healthcare costs are reduced. However, despite overwhelming evidence of the positive impact pharmacists can have on patient health, pharmacists are not currently recognized as healthcare providers under the Social Security Act and, therefore, cannot be paid by Medicare for therapy management and patient consultation services. The Social Security Act does recognize other healthcare professionals such as dieticians, nurse practitioners, physician assistants, nurse midwives, and clinical social workers.

Thanks to Medscape News;

The Impact of Snacking on Children's Health

According to a recent study, children in the United States are snacking more than they did 20 years ago. Currently, about 90% of children snack daily, up 10% from the 1970s. Snacking itself will not necessarily lead to obesity, but increased rates of snacking and the types of snack food have contributed to the weight-gain trend in US children. When compared to regular meals, the current snacks provide less calcium, more energy, and a higher proportion of energy from fat.

The study was published in the April issue of the Journal of Pediatrics, analyzing data from 21,000 children aged 2 to 18 years. The data came from the 1977-78 Nationwide Food Consumption Survey and both the 1989-91 and 1994-96 editions of Continuing Survey of Food Intake by Individuals. Over the last 20 years, the proportions of overweight schoolchildren and adolescents have increased from 8% to 14% in children and from 6% to 12% in adolescents. Because of the adverse effects of obesity on risk of diabetes and cardiovascular disease, the researchers attempted to determine whether the snacking habits of US schoolchildren had changed over time.

The "energy density" of the snacks (kcal per gram) have increased from 1.35 to 1.54, a statistically significant increase. More importantly, additional researchers have found small increases in energy densities lead to a large increase in total energy. Energy-dense foods are snacks with high caloric content but low nutritional value. These include soft drinks, potato and corn chips, and other salty snacks. Energy dense foods don't reduce appetite as much as healthier foods do.

The study found that the biggest increase in snacking occurred during the last decade, reflecting corresponding increases in obesity among US children. Previous decades showed smaller changes in snacking habits and weight gain. An important step in eliminating "junk foods" from the snack diet is removing soda and candy machines from schools and replace them with healthier items, a step that many school districts are currently taking nationwide.

Journal of Pediatrics. 2001;138(4):493-498

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