Smallpox Vaccination Guidelines Published by CDC

Pharmacology Watch

The Centers for Disease Control and Prevention published "Smallpox Vaccination and Adverse Reactions—Guidance for Clinicians" in the Jan. 24th edition of Morbidity and Mortality Weekly Report. The guidance is a thorough review of the smallpox vaccine with a well-illustrated compendium of complications. Some of the highlights include:

Inoculation is administered using a multiple-puncture technique with the bifurcated needle. The inoculation site progresses from papule to vesicle, eventually becoming a pustule within 10 days. The pustule scabs over within 2-3 weeks usually leaving a pitted scar. Development of a pustular lesion is considered a major reaction and a successful vaccine take. Lesser reactions are considered equivocal and are nontakes. Large vaccination reactions may occur in 10% of first-time vaccinees. Systemic reactions are common in all vaccinees and include fatigue, headache, myalgias, chills, nausea, and fever. The vaccine is made from live vaccinia virus (it does not contain variola virus) and transmission is possible from the vaccination site up to 3 weeks after vaccination. The shedding period may be less for revaccination. The inoculation site is generally considered infectious from the time just after vaccination until the scab separates from the skin. Vaccinia is transmitted by close contact and can lead to the same adverse events in an infected contact as in the vaccinee. The inoculation sites should remain covered and vaccinees should wash their hands immediately after touching vaccination sites or changing dressings. The smallpox vaccination is generally considered safe, but is contraindicated in patients who have, or are in close contact with, those who have atopic dermatitis (eczema) regardless of the severity, skin diseases that disrupt the epidermis, pregnant women or women who plan on becoming pregnant within 1 month after vaccination, and immunocompromised patients. Others who should not receive the vaccine include those who have an allergy to a component of the vaccine, are breast-feeding, are using ocular steroids, have moderate-to-severe intercurrent illness, or are younger than 18 years of age.

The CDC has an excellent web site for health-care providers who wish to learn more about the smallpox vaccine: www.bt.cdc.gov/training/smallpoxvaccine/reactions/default.htm

Nurses: Delay Vaccination Program

Meanwhile, not everyone is happy with the national smallpox vaccination program. Recently the American Nurses Association (ANA) requested that the Bush administration delay the smallpox vaccination program until certain safety issues can be addressed. Specifically, the ANA is seeking information regarding potential transmission of vaccinia virus to family members of vaccinated nurses, coverage of medical costs related to vaccination, safety of the vaccination materials, adequate educational materials and staffing issues, and job security issues related to the vaccination program. Others such as Thomas Mack, MD, MPH, argue in the Jan. 30 edition of the New England Journal of Medicine that smallpox is overrated as a bioterrorist weapon. His view is that the current vaccination policy would provide little protection and the cost from vaccine complications would outweigh any benefit (N Engl J Med. 2003;348:460-463). However, a special article in the same issue developed scenarios of smallpox attacks and reviewed possible outcomes of control policies. Their analysis favors a program of prior vaccination of health care workers but favors vaccination of the public only in the likelihood of a national attack, or multiple attacks is very high (N Engl J Med. 2003;348:416-425).

Viagra Effective for Depression Treatment

Sildenafil (Viagra) is an effective treatment for antidepressant-associated sexual dysfunction in men. The drug was tested in a multicenter randomized double-blind placebo-controlled trial. Ninety men with major depression in remission on SSRI antidepressants were randomly assigned to take sildenafil (50 to 100 mg) or placebo for 6 weeks. Men who were most affected by antidepressant-associated sexual dysfunction were significantly more likely to improve with sildenafil (24/44, 54.5% response rate) vs placebo (2/45, 4.4% response rate) (P < .001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction measures improved significantly with sildenafil compared with placebo (JAMA. 2003;289:56-64). This study is important because sexual dysfunction is a common cause of noncompliance with serotonin reuptake inhibitors, and use of sildenafil may improve compliance with antidepressant treatment.

Finisteride/Doxazosin no Better than Placebo for Urinary Obstruction

Finisteride (Proscar) is no better than placebo when used in combination with doxazosin for the treatment of urinary obstruction due to benign prostatic hypertrophy, according to the recently published Prospective European Doxazosin and Combination Therapy (PREDICT) trial. These findings come in contradiction to the Medical Therapy of Prostatic Symptoms (MTOPS) trial published in May 2002, which showed a benefit of the combination of finasteride and doxazosin. In the current study, more than 1000 men were randomized to doxazocin, finisteride 5 mg per day, the combination of both, or placebo. The groups receiving doxazocin alone or in combination with finisteride had significant improvements in total maximal urinary flow rates and International Prostate Symptoms Score compared to the finisteride alone group and placebo group (P < .05). There was no significant difference between treatment with finisteride and placebo. Doxazosin was initiated at 1 mg per day and titrated to a maximum of 8 mg per day. All treatments were well tolerated (Urology. 2003;61:119-126).

Sildenafil, however, may be effective of relieving obstructive urinary symptoms in men who use the drug on a regular basis. British researchers looked at 112 men with erectile dysfunction at 1 and 3 months after taking sildenafil as needed before sexual intercourse. Only 20 of the 112 men complained of lowered urinary tract symptoms, but of those men, improved urinary scores at 3 months strongly correlated with improvement in sexual function. The authors suggest that an increase in nitric oxide associated with the resumption of normal sexual activity may be responsible for the improvement in urinary symptoms (Br J Urol Int. 2002;90: 836-839).

Serevent Receives Dear Doctor’ Letter

GlaxoSmithKline has issued a "Dear Doctor" letter regarding its asthma bronchodilator salmeterol (Serevent). The warning is based on interim results from a large study of salmeterol that was initiated in 1996. The Salmeterol Multi-center Asthma Research Trial (SMART) was a postmarketing study designed to investigate reports of several asthma deaths associated with use of salmeterol. Analysis of the interim results showed a trend "toward a greater increase in asthma deaths and serious asthma episodes" with the largest increase in African-American patients. Data on almost 26,000 patients were available for analysis. While there was no significant difference for the primary end point of combined respiratory related deaths and respiratory related life-threatening experiences including incubation and mechanical ventilation between salmeterol and placebo, a higher, but not statistically significant number of asthma related life-threatening experiences including deaths occurred in the salmeterol group. The number of adverse events reached statistical significance in African-Americans who represented 17% of the study. No other ethnic group drew any conclusions. The use of inhaled corticosteroids reached only 47% in the entire population of the SMART study. Because of these findings, GlaxoSmithKline has decided to discontinue the study and continue reviewing data from the interim analysis. The FDA is involved in this process and will likely require label changes for Serevent that will reinforce guidance on appropriate and safe prescribing. 


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) 262-5517. E-mail: robin.mason@ahcpub.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.