Nasally Administered Flu Vaccine Comes to United States
Pharmacology Watch

The FDA has approved the first nasally administered flu vaccine to be marketed in this country. Medimmune’s "FluMist" is also the first influenza vaccine to use live virus. This year’s version of the vaccine contains 3 attenuated viruses (trivalent) that are temperature sensitive and replicate in the nasopharynx. FluMist is approved for children aged 5-17 and healthy adults aged 18-49. Children aged 5-8 require 2 doses at least 6 weeks apart whereas older patients only require 1 dose. The Centers for Disease Control are not recommending FluMist for high-risk patients, children younger than 5 years old, or adults older than age 65. For these patients, the CDC recommends standard influenza vaccine. Children younger than age 5 were found to have an increased rate of asthma and wheezing within 1 month of receiving FluMist. Therefore, the vaccine is not recommended for children younger than age 5 or for those with asthma or other reactive airway disease. FluMist should be available this fall.

Paxil: Not Recommended for Children

The FDA is recommending that paroxetine (Paxil) not be started in children and adolescents for the treatment of major depressive disorder (MDD) because of the potential risk of increased suicidal thinking and suicide attempts. In an FDA Talk Paper published June 19, the agency said it is reviewing reports of increased risk of suicide in children younger than age 18 treated with Paxil. The paper also states that there is no current evidence of Paxil’s effectiveness in children or adolescents with MDD, and other approved treatment options are available. The advisory urges patients not to stop Paxil abruptly, however, because of the risk of withdrawal symptoms that are somewhat unique to the drug. More information is available at

Prilosec Granted OTC Status

The FDA has approved omeprazole (Prilosec) for over-the-counter use for the treatment of frequent heartburn. Prilosec OTC, as the product is being called, is a 20-mg delayed-release tablet that should be taken once a day for 14 days. The 2-week course is recommended because of data suggesting that the effectiveness of Prilosec OTC increases from day 1 to day 14. It is only indicated for heartburn that occurs 2 or more days per week. Prescription Prilosec will also remain available, and while generic omeprazole is available in the prescription market, only AstraZeneca will have approval to market OTC omeprazole for 3 years because of an exclusivity agreement.

Finasteride and Prostate Cancer

Finasteride reduces prostate cancer risk, but at a price. The National Cancer Institute (NCI) decided on an early termination of the Southwest Oncology Group Prostate Cancer Prevention Trial (PCPT) when it was found that finasteride 5 mg/d reduced the rate of prostate cancer. In this study, men aged 55 and older with a normal digital rectal exam (DRE) and a PSA of < 3.0 were randomized to finasteride or placebo for 7 years. Prostate biopsies were performed if the PSA reached 4 or higher or if DRE revealed an abnormal prostate. After 7 years, 803 of the 4368 men in the finasteride group developed prostate cancer (18.4%) as compared to 1147 of the 4692 men in the placebo group (24.4%), for a 24.8% reduction in prevalence over the 7-year period (95% CI, 18.6-30.6%; P < .001). More aggressive tumors, however, were found in the finasteride group (280 of 757 tumors, Gleason grade 7, 8, 9, or 10 [37.0%] vs 237 of 1068 tumors in the placebo group [22.2%]; P < .001). Sexual side effects were also more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo. Mortality was not assessed. The authors state that "finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer" (Published at Accessed June 24, 2003; final publication due July 17, 2003). An accompanying editorial urges caution in interpreting these results and does not recommend wholesale use of finasteride for chemoprotection of prostate cancer, arguing that the drug may only protect against low-grade cancers and that more research is needed.

Xolair: First Biologic Agent for Asthma

The FDA has approved omalizumab (Xolair), the first biologic agent for the treatment of asthma. The drug is a humanized antibody that targets circulating IgE, decreasing the amount of IgE antibodies available to bind mast cells, thus making mast cells less available to release mediators of inflammation. Omalizumab is indicated for adults and adolescents, 12 years of age and older, with moderate-to-severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids. The drug is considered a maintenance medication and is not indicated for acute asthma attacks. Initial studies have shown that the drug reduces the rate of asthma exacerbations and cuts down on emergency room visits. It has not been tested for other allergic conditions. Omalizumab is an injectable medication that must be given once or twice a month. The cost is more than $400/vial with an estimated yearly cost of $10,000 to $12,000. Side effects include malignancies that were seen slightly more often with the drug (0.5% omalizumab vs 0.2% placebo). Naphylactic reactions occurred, but were rare (< 0.1%). The drug, which is being comarketed by Genentech and Novartis, should be available mid 2003.

West Nile Virus Update

The West Nile virus has killed 284 people in North America and has been detected in 44 states. It now represents the most significant arbovirus outbreak in this country’s history. Now Dutch biotechnology company Crucell is ready to start testing a West Nile virus vaccine in humans and will announce clinical development timelines later this year. The virus, which is reservoired in birds and transmitted by mosquitoes causes fatal encephalitis in a small minority of infected patients. Currently, the only protection against the disease is protection against mosquito bites. Crucell has conducted preclinical studies in geese animal models with an experimental vaccine demonstrating disease-free survival after a lethal challenge to the virus.

Study Shows COX-2 Inhibitors Appear Safe with Aspirin in Asthma Patients

COX-2 inhibitors appear to be safe in patients with aspirin-sensitive asthma, according to a new study. In a multinational study 33 patients with aspirin-intolerant asthma were tested for tolerance of the COX-2 inhibitors celecoxib in a double-blind, randomized, crossover fashion. There were no changes in lung function or extrapulmonary symptoms with celecoxib, even at the highest recommended daily dose of the drug. The authors conclude that aspirin-intolerant asthma, which generally includes other nonspecific NSAIDs, is a COX-1 effect and that COX-2 inhibitors may be safe in this group, although further studies are needed (J Allergy Clin Immunol. 2003;111:1116-1121).

Lamictal Approved for Bipolar Disorder

Lamotrigine (Lamictal) has been approved for maintenance treatment of adults with bipolar I disorder. The drug, which was previously approved for partial seizures, becomes the first FDA- approved therapy since lithium for this disorder.

Two studies presented to the FDA showed a benefit for lamotrigine in delay in time to occurrence of both depression and mania, although the effect was more robust for depression.

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: 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.