The Food and Drug Administration and Centers for Disease Control are currently working closely with influenza vaccine manufacturers to facilitate the availability of a safe and effective influenza vaccine for the upcoming flu season. Influenza vaccine manufacturers have told FDA and CDC to expect delays in flu vaccine shipments, and that it is possible there will be reductions of available influenza virus vaccine for the 2000-01 season.

The Advisory Committee on Immunization Practices (ACIP) is urging health care providers to consider delaying mass adult influenza vaccination campaigns to November based on supply availability and to consider ways to ensure that high risk patients receive vaccination if a severe vaccine shortfall were to occur. Although the total amount of vaccine available is uncertain, both FDA and CDC are actively working with manufacturers to determine how much and when vaccine will be available. The amount of available flu vaccine will become more clear within the next two months.

Health professionals who are potential flu vaccine providers should adequately prepare for the upcoming season. Patients who normally receive influenza vaccine should not be concerned and should delay inquiries about flu vaccination until the fall. It should be stressed that FDA and CDC are confident that vaccine will be available to vaccinate those at highest risk of complications from influenza, including those over 65 and immunosuppressed patients.

If a significant shortfall of vaccine were to occur, the ACIP and CDC would modify recommendations for the 2000-2001 influenza season, emphasizing vaccinating patients at highest risk of death from influenza (and the health care workers who take care of them). Other groups for whom vaccine is traditionally recommended should then be vaccinated as the vaccine supply allows.

CDC News Release http://www.cdc.gov/

The World Health Organization estimates that more than 170 million individuals throughout the world are infected with the hepatitis C virus (HCV). In North America, the prevalence of chronic hepatitis C infection is 1.8%. Prevalence rates as high as 20% have been found in Egypt. HCV is usually transmitted by percutaneous exposure to blood and most new infections in developed countries are related to drug use. Transmission through folk and alternative medical procedures or cultural practices such as acupuncture has been reported in pre-developed countries.

A large number of individuals with chronic HCV have no known risk factors, making diagnosis of the disease even more difficult. A recent study in England reported that nearly 40% of patients had no known risk factor for infection. HCV infection is subclinical in the majority (70% to 80%) of cases. Of those who develop acute hepatitis as a result of HCV infection, up to 91% go on to develop chronic hepatitis. Chronic infection may or may not be accompanied by alanine transaminase (ALT) abnormalities and persistent or intermittent viremia.

The only therapies for HCV infection currently approved include Alpha interferon (IFN-alpha) alone or in combination with oral ribavirin. Combination therapy is rapidly replacing interferon monotherapy because dual therapy is significantly more effective. Forty percent of patients treated with IFN-alpha alone have an initial response characterized by normalization of liver function tests and loss of detectable HCV RNA. However, most patients relapse after therapy.

Treatment with interferon leads to a variety of side effects that can significantly impair quality of life. Some clinical trials suggest that over 60% of patients treated with IFN have influenza-like symptoms. Other common and disabling side effects are chronic fatigue and depression. Short courses of IFN are relatively well tolerated, but increasing the duration of therapy from 6 to 12 months increases the incidence of side effects.

Current therapy for chronic HCV infection is clearly unsatisfactory as only 40% of patients respond to therapy, and the side effects are considerable. Recent developments in IFN technology have led to longer-lasting IFNs that consist of IFNs linked to polyethylene glycol. These new "pegylated" IFNs are available in a variety of different molecular sizes, and it is clear that these different PEG-IFNs also have different properties and effects. Clinical trials of the new PEG-IFNs are now underway and recent data show that 12-kD PEG-IFN-alpha 2b leads to response rates of 25% in patients with chronic hepatitis C and monotherapy with the 40-kD PEG-IFN-alpha 2a produced a sustained response rate of nearly 40%.

Infection with HCV is a very common clinical problem that often leads to liver cirrhosis and cancer. The current treatment strategy has a high incidence of side effects and leads to a sustained virologic response in a small proportion of patients. Studies involving these two novel pegylated IFNs in combination with ribavirin are now ongoing and the results from these important trials are anxiously awaited.

Major depression (MD) is the most common of all psychiatric disorders. According to the National Comorbidity Survey, 17.1% of the general population in the United States have a lifetime history of a major depressive episode, and 10.3% have had an episode in the past 12 months. With the exception of hypertension, MD is more commonly encountered than any other condition in the primary care setting. It is also associated with markedly higher health care costs than other common disorders seen in primary care.

MD is one of the 15 leading causes of disability in developed countries and will become the second leading cause of disability worldwide by 2020. The WHO deemed the degree of disability associated with depression to be greater than that associated with other chronic conditions, such as hypertension, diabetes, arthritis, and back pain. MD is also associated with high morbidity and mortality; up to 15% of individuals with more severe forms of this disorder die by suicide. The prevalence, disability burden, economic toll, morbidity, and mortality associated with MD call for increased attention to this disorder among pharmacists and other health care providers.

A recent analysis in the Journal of the American Pharmaceutical Association reported epidemiological data from several cultures, indicating that the lifetime prevalence of major depression is twice as high in women as in men. MD a multifactorial disorder that is influenced by numerous risk factors, including age, socioeconomic status, childhood history of sexual abuse, and recent stressful life events. Women often experience different types of depression during various reproductive or life stages, including premenses, pregnancy, postpartum, and menopause.

Treatment for major depression includes psychosocial therapy, pharmacotherapy, and electroconvulsive therapy. The literature indicates that major depression is often underrecognized and undertreated. Biological and psychosocial factors contribute to the higher vulnerability of women to major depression. This behooves a multidimensional approach to treatment. The primary role of the health care provider is recognition of the disease by its signs and symptoms and to provide education about this disease. Patients presenting with signs and symptoms of depression should be referred for evaluation. By encouraging appropriate use of antidepressants, pharmacists can improve the detection and treatment of major depression.

Nonsteroidal anti-inflammatory drugs (NSAIDs) block inflammatory responses by inhibiting cyclooxygenase (COX), which prevents prostaglandin synthesis. The

COX-1 isoenzyme is constitutively expressed and is involved in the synthesis of prostaglandins that protect the gastrointestinal mucosa. In contrast, COX-2 expression is inducible, and is responsible for the generation of prostaglandins that mediate inflammatory responses. Selective COX-2 inhibitors block inflammatory cascades without many of the side effects of nonselective NSAIDs that result from concurrent inhibition of COX-1.

Cannon and colleagues recently performed a randomized, double blind, controlled trial of rofecoxib (a COX-2 inhibitor) vs. a nonselective NSAID (diclofenac) for the treatment of osteoarthritis (OA). Data from the study indicate that rofecoxib and diclofenac are comparable in their clinical efficacy in the treatment of OA and that diclofenac treatment was associated with a higher incidence of elevated serum aminotransferase levels.

In another recent trial, Langman and colleagues assessed gastrointestinal toxicity in eight double blind, randomized clinical trials of rofecoxib for the treatment of osteoarthritis. The analysis included more than 5000 patients. The cumulative 12-month incidence of confirmed episodes of gastroduodenal ulcer and upper gastrointestinal bleeding was significantly lower in the rofecoxib group compared with the NSAID group. Analysis of placebo-controlled trials revealed that the relative risk of gastroduodenal ulcer and upper-gastrointestinal bleeding over 4 months was 2.50 for NSAIDs vs. placebo and 0.94 for rofecoxib vs. placebo.

Data from these two recent trials indicate that the risk of serious gastrointestinal toxicity from NSAIDs is relatively low over a 12-month period, and that this risk can be reduced to levels indistinguishable from those observed in patients on placebo by using a selective COX-2 inhibitor such as rofecoxib.

(2) Fauci AS; Rofecoxib for the Treatment of Osteoarthritis http://www.medscape.com/

New FDA Drug Applications Approved in August

Cetrotide^® is an injectable form of cetrorelix that is under development by Asta Medica Inc. It is proposed for the prevention of premature LH surges in women undergoing controlled ovarian stimulation.

Children’s Motrin Cold^® medication is an over the counter preparation of Ibuprofen and Pseudoephedrine HCL that is utilized for the temporary relief of nasal and sinus congestion, minor body aches and pains, fever, stuffy nose, headache, and sore throat in children. It is manufactured by McNeil Consumer Healthcare, Inc.

Depakote ER^® is a new prescription medication for the prophylaxis of headaches in adults. Depakote is the tablet form of Divalproex sodium and is produced by Abbott Laboratories.

Rescula^® is an eyedrop solution by Ciba Vision Corporation, a division of Novartis. It is a prescription form of unoprostone isopropyl, used to lower intraocular pressure in patients with open-angle glaucoma or ocular hypertension and who are intolerant of other intraocular pressure lowering medications. It is targeted for patients who have failed to achieve target IOP determined after multiple measurements over time using another intraocular pressure lowering medication.

Concerta^® is an extended release tablet form of methylphenidate HCL that is used for the treatment of attention deficit disorder. It is still under study at Alza Corporation.

FDA Drug Approvals List at http://www.fda.gov/cder/

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