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Antiviral Medications Not Associated with Birth Defects
In this issue: Antiviral drugs and birth defects, bisphosphonates and esophageal cancer, naltrexone plus bupropion for weight loss, 2010-11 influenza vaccine, FDA Actions.
Antivirals not associated with birth defects
Young women with herpes infections are often treated with the oral antivirals acyclovir, valacyclovir, or famciclovir. A new study suggests that these drugs are relatively safe when taken in the first trimester of pregnancy. A population-based historical cohort study was performed reviewing the records of more than 800,000 liveborn infants in Denmark who had no diagnosis of chromosomal aberrations, genetic syndromes, birth defects syndromes with known causes, or congenital viral infections. There were 1804 pregnancies exposed to acyclovir, valacyclovir, or famciclovir in the first trimester. Of those, 40 infants (2.2%) were diagnosed with major birth defects compared with 19,920 (2.4%) among the unexposed infants (adjusted POR, 0.89; 95% CI, 0.65-1.22). Broken down by drug, major birth defects were seen with 2% of infants exposed to acyclovir and 3.1% exposed to valacyclovir; exposure to famciclovir was uncommon. There was no association between antiviral drugs and specific types of birth defects. The authors conclude that exposure to acyclovir or valacyclovir in the first trimester of pregnancy was not associated with an increased risk of major birth defects (JAMA 2010;304:859-866).
Bisphosphonates and esophageal cancer
Oral bisphosphonates are not associated with an increased risk of esophageal cancer according to a new study from the U.K.'s Centre for Public Health and the National Institutes of Health. Concern was raised regarding a possible link between bisphosphonates and esophageal cancer after a letter from the FDA was published in the New England Journal of Medicine in January 2009 describing 23 patients with a diagnosis of esophageal cancer who had been taking alendronate (N Engl J Med 2009;360:89-90). Data from the U.K. General Practice Research Database between 1996 and 2006 were reviewed. There were nearly 42,000 patients who received bisphosphonates during that time frame who were compared to the same number of control patients. There were 116 esophageal or gastric cancers, of which 79 were esophageal, in the bisphosphonate cohort, and 115 cancers, of which 72 were esophageal, in the control cohort. The incidence of esophageal cancer was 0.48 per 1000 person-years of risk in the bisphosphonate group and 0.44 in the control group. Similarly, there was no difference in the rate of gastric cancer between the two groups. There was also no difference in cancer incidence in a subgroup analysis reviewing specific types of bisphosphonates, as well as analysis limited to patients with GERD or Barrett's esophagus. The authors conclude that use of oral bisphosphonates was not significantly associated with incidence of esophageal or gastric cancer (JAMA 2010;304:657-663).
Naltrexone plus bupropion for weight loss
Naltrexone plus bupropion may be an effective adjunct to lifestyle changes in patients attempting to lose weight. Men and women (n = 1742) age 18-65 with BMIs of 30-45 kg/m2 and uncomplicated obesity, or BMIs of 27-45 kg/m2 with dyslipidemia or hypertension, were enrolled at 34 sites across the United States to receive extended-release naltrexone 32 mg plus sustained-release bupropion 360 mg, sustained-release naltrexone 16 mg plus sustained-release bupropion 360 mg, or matching placebo twice a day for 56 weeks. Mean body weight changes were -1.3% in the placebo group, -6.1% in the naltrexone 32/bupropion group (P < 0.0001 vs placebo), and -5.0% the naltrexone 16 mg/bupropion group (P < 0.0001 vs placebo). Significantly more patients in the active drug categories had a greater than 5% decrease in body weight (16% placebo, 48% naltrexone 32 mg/bupropion, 39% naltrexone 16 mg/bupropion, both significant at P < 0.0001 vs placebo). Nausea was significantly more likely to occur in both active treatment groups. A transient increase of blood pressure of 1.5 mmHg in mean systolic and diastolic pressures was noted in the treatment groups, followed by a reduction of 1 mmHg below baseline by the end of the study. No psychological side effects were noted with the active treatment group. The authors conclude that a sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity (Lancet 2010;376:595-605). This was a phase 3 study funded by Orexigen Therapeutics, which is currently developing a naltrexone SR/bupropion SR combination under the trade name "Contrave."
2010-11 influenza vaccine
The CDC's Advisory Committee on Immunization Practices has published its recommendations for the 2010-11 influenza vaccine. The trivalent vaccine will contain A/California/7/2009 (H1N1)-like (the same strain that was used with a 2009 H1N1 monovalent vaccine) as well as A/Perth/16/2009 (H3N2)-like and B/Brisbane/60/2008-like antigens. The CDC has significantly expanded the population it recommends receive the vaccine. In previous years, annual vaccination was recommended for all adults ages 19-49 years, whereas now the recommendation is that all persons aged 6 months and older should get a flu vaccine as soon as it is available this fall. Children ages 6 months to 8 years who did not receive at least one dose of the 2009 H1N1 vaccine should receive 2 doses of the 2010 seasonal vaccine. Vaccine is being produced by at least 6 different manufacturers, although different manufacturers have different age range approvals. Sanofi Pasteur has received approval for its high-dose inactivated trivalent vaccine for adults ages 65 and older ("Fluzone High Dose"). It is anticipated that vaccine will be in plentiful supply this fall and will be ready for distribution early in the season.
The FDA has proposed the withdraw approval of the drug midodrine hydrochloride. Midodrine was approved in 1996 under the FDA's accelerated approval regulation to treat orthostatic hypotension. The FDA requires post-approval studies to verify the clinical benefit of such drugs, but these studies were never done. Shire Pharmaceuticals, manufacturer of brand-name ProAmatine® (midodrine), has announced plans to remove the drug from the market effective September 30. Generic manufactures have not announced their plans of action as yet. The FDA advises patients who are currently taking midodrine to continue it until they can consult their health care professional about other treatment options.
The FDA has approved a new emergency contraceptive for use within 120 hours (5 days) after failure of standard contraception or after unprotected intercourse. The so called "5 day after pill" contains ulipristal acetate, a progesterone agonist/antagonist that likely works by inhibiting or delaying ovulation. The drug is taken as a single tablet and is available only by prescription. Ulipristal acetate is manufactured by Paris-based Laboratoire HRA Pharma and will be marketed under the trade name "Ella."
An FDA advisory panel has recommended against approval of sodium oxybate for the treatment of fibromyalgia. The controversial drug, also known as GHB, has gained notoriety as a "date rape" drug. The panel felt that the risk for widespread abuse was too great to warrant extending indication to fibromyalgia, a condition that affects up to 2% of the U.S. population. Many panel members also felt that Jazz Pharmaceuticals who currently markets sodium oxybate under the trade name "Xyrem" for the treatment of narcolepsy and cataplexy, did not convincingly show that the drug was effective for the treatment of fibromyalgia.
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. 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. Questions and comments, call: (404) 262-5468. E-mail: email@example.com.