Missing Link Between Vaccines and Diabetes

Pharmacology Watch

A large cohort study from Denmark suggests no link between childhood vaccines and type 1 diabetes. The potential for such a link has been of concern for years because of the association between certain infections and the development of type 1 diabetes in children. Epidemiologists also noted that the incidence of type 1 diabetes has increased in developed countries along with a widespread use of vaccines in those countries. Danish researchers studied the records of children born in Denmark between 1990 and 2000, which represented 4,720,517 person-years of follow-up. In the cohort, 681 cases of type 1 diabetes occurred. The rate ratios for developing diabetes among children who received at least 1 vaccine compared to unvaccinated children were: 0.91 for Haemophilus influenzae type B vaccine, 1.02 for diphtheria/tetanus/polio vaccine, 0.96 for diphtheria/tetanus/pertussis/polio vaccine, 1.06 for whole cell pertus! sis, 1.14 for measles/mumps/rubella vaccine, and 1.08 for oral polio vaccine. No clusters of diabetes cases were found at any age level. The authors conclude that the data do not support the causal relationship between childhood vaccine and type 1 diabetes (N Engl J Med. 2004; 350:1398-1404).

Breast Cancer and the Use of Statins

Adding to the considerable evidence regarding the safety and efficacy of statins, it now appears that statins may slightly reduce the risk of breast cancer. Published in the "Early View" online journal Cancer, this case-control study was designed to assess whether statins were associated with an increased risk of breast cancer. At least 1 previous study has suggested an increased risk of breast cancer with statin use. The study looked at 975 women in Washington state who were diagnosed with primary invasive breast carcinoma, and were between 65 and 79 years old at the time of diagnoses. The comparison group was 1007 randomly selected women from the same residence area. Compared with non-users, current users, or ever-users of statins were not found to be at an increased risk for breast carcinoma. And in fact, the odds ratio of statin users was 0.9 compared to non-statin users (95% CI, 0.7-1.2). Long-term statin use of > 5 years was related to an even lower odds ratio of 0.7. The authors conclude that statins are not associated with an increase risk of breast carcinoma, and may in fact impart a reduced risk among long-term users (Cancer April 26, 2004).

Warnings Issued for IBS Drugs

Tegaserod (Zelnorm-Novartis), the heavily promoted serotonin 5-HT4 partial agonist for the treatment of irritable bowel syndrome (IBS), is the subject of new warnings by the FDA. The drug is indicated for women with IBS whose primary symptom is constipation. The warning is the result of reports of diarrhea leading to hypovolemia, hypotension, and syncope in a small number of patients. There have also been rare cases of bowel ischemia in patients taking tegaserod, although no causal relationship has been found. Novartis has issued a "Dear Doctor" letter regarding the change in labeling dated April 26 (for more information see www.FDA.gov/medwatch). This is the second IBS drug to come under FDA scrutiny. The serotonin 5-HT3 antagonist alosetron (Lotronex-GlaxoSmithKline), for the treatment of IBS in women with severe diarrhea, was briefly withdrawn from the market in June 2002 because of over 80 cases of ischemic colitis associated with use of the drug. Alosetron became available again in December 2002 under a restricted use program.

What is the risk of a re-prescribing penicillin to penicillin allergic patient? The risk may be quite low according to a new study. Researchers looked at a database from the UK General Practice Research Database which included over 3.3 million patients who received penicillin. More than 6000 patients reported an allergy to the initial prescription, however, 48.5% of those patients were given the second prescription for penicillin at least 60 days later. Of those 3014 patients, only 57 (1.89%) had another event after the second prescription. This was much higher than the rate of reactions in patients who had not had an initial reaction (odds ratio, 11.2; [95% CI 8.6-14.6]), however, the absolute rate of reactions in patients who had an initial allergic reaction was quite small (J Allergy Clin Immunol.2004:113; 764-770). An accompanying editorial pointed out that even anaphylactic reaction had a low rate of recurrence with repeat exposure (1 out of 16) (J Allergy Clin Immunol.2004:113;605-606). And, while no one is recommending rechallenging patients with penicillin allergies, the low rate of repeat reactions is a far cry from the reported 60% rate of previous studies

FDA Actions

The FDA has removed the warning for lactic acidosis from metformin (Glucophage) and metformin extended release (Glucophage XR). Once considered the most serious side effect associated with metformin, a recent meta-analysis showed that there were no reports of lactic acidosis during more than 20,000 patient years use of the drug (Arch Intern Med.2003;163:2594-2602).

The FDA has approved apomorphine injection (Apokyn-Bertek) for hypomobility associated with Parkinson's disease. Hypomobility or "off periods" become more frequent with advanced Parkinson's disease and may occur at the end of a dosing interval or may occur spontaneously. A subcutaneous injection of apomorphine is effective for both types of "off periods." However, because the drug causes severe nausea, it must be taken with an anti-emetic—although, not a 5HT3 antagonist because the combination may cause hypotension and syncope.

Aventis has received approval to market insulin glulisine (Apidra), a new rapid-acting insulin. The drug is a novel recombinant DNA human insulin analogue that is designed to be given 15 minutes before a meal or within 20 minutes after starting a meal. With a rapid onset and short duration of action, it is designed to cover mealtime blood sugar spikes. Aventis is marketing insulin glulisine to be used in combination with insulin glargine (Lantus), the company's long-acting basal insulin preparation.

The FDA has approved changes in prescribing information for finasteride (Proscar-Merck) that include concomitant use of the alpha-blocker doxazosin for the treatment of benign prostatic hyperplasia. Finasteride is a 5-alpha-reductase inhibitor. The combination was recently found to be better than either drug alone in reducing the overall clinical progression of benign prostatic hyperplasia (NEng J Med.2003;349:2387-2398).

Telithromycin (Ketek-Aventis) has been approved by the FDA for marketing for the treatment of community-acquired pneumonia including pneumonia caused by drug-resistant pneumococcus, sinusitis, and acute exacerbations of chronic bronchitis. Telithromycin represents the first of a new class of antibiotics known as ketolides. It is an oral tablet that is given once a day.

This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. Telephone: (404) 262-5413. E-mail: christie.petrone@thomson.com. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.