Abstracts of Interest
Many of the following abstracts result from inquiries we have received from clients and health professionals worldwide. Past abstracts for 2000 and 2001 available.
Asthma
The inhaled corticosteroid fluticasone propionate resulted in lower asthma care costs than use of the oral leukotriene receptor antagonist montelukast or zafirlukast. Patients started on inhaled corticosteroids were less likely to require the addition of a second controller or to be switched to another controller than those first started on a leukotriene modifier. However, patients that received an inhaled corticosteroid had less severe disease. This discrepancy between groups was accounted for, but the differences may have still affected the results. The time to switch to or add another controller drug was significantly longer in the fluticasone group even though adherence was significantly lower in this group. The findings suggest greater effectiveness of inhaled corticosteroids. Pharmacotherapy 2002;22:148-153.
Cardiology
NSAIDS such as ibuprofen should be used cautiously if at all in patients with heart failure. A recent study found that disease relapse is nearly 10 times more likely in patients that use a NSAID. In contrast, the risk of developing heart failure did not differ between patients that did and did not use NSAIDS. Arch Intern Med 2002;162:265-270.
Dermatology
There are many options for treatment of lice. In a study done in the U.S., Ovide lotion (0.5% malathion) was the most effective followed, in order of effectiveness, by A-200 shampoo (a natural pyrethrin product synergized with piperonyl butoxide), undiluted Nix (1% permethrin), diluted Nix, RID (a natural pyrethrin product synergized with piperonyl butoxide), and 1% lindane shampoo. Some lice will not be killed by any given product. Watch for scalp irritation and infection. Treatment with another product or method may be needed. Arch Dermatol 2002;138:220-224.
Diabetes
Assessment of the fasting glucose level is recommended every three years for everyone over age 45 years. Earlier and more frequent assessment is recommended for patients at a higher risk of diabetes. These patients include African Americans, Native Americans, Mexican Americans, those with a family history of diabetes, and patients with obesity, hypertension, dyslipidemia, or history of gestational diabetes. Maintenance of a healthy body weight and can help prevent and treat diabetes. The ideal body weight is calculated by adding five pounds for every inch over five feet to 100 pounds in a woman and adding six pounds for every inch over five feet in a man. Ten percent should be added or subtracted for a large or small frame, respectively. Improved control of diabetes can occur with as little as a 5% loss of body weight. In addition to lowering the amount of calories taken in, exercise is very important to help with weight loss. Exercise also helps to improve insulin resistance (helps insulin work in the body).
Drug Information
Information available on the internet may not be accurate. Anyone can post information to the internet and the information may be outdated. Several factors can help discern the quality of available information including who is the presenter of the information, the revision date of the information, and the presence of a disclosure statement. Regardless of how official information may be seen, it is usually best to obtain information directly from your health care professional. Brit Med J 2002;324:577-583.
Gynecology
The risk of stroke, heart attack, blood clots, and breast cancer associated with oral contraceptive pill use in women under the age of 35 is low. Women who are over age 35 and who smoke should not use estrogen-containing oral contraceptive pills to minimize the potential risk of a heart attack and stroke. The use of low-dose oral contraceptives in women at low risk for stroke (normal blood pressure and nonsmokers) appears to have minimal effects on the risk of stroke and should be considered safe. The risk of developing a blood clot is higher (but still low overall) for women who become pregnant and may be higher for those who are on a product containing desogestrel or gestodene. There may be an increased risk of breast cancer in women under age 35 years who use an oral contraceptive pill for many years, but the overall risk is low due to the low incidence of breast cancer in this population. Semin Reprod Med 2001;19(4):305-312.
Patients who use oral contraceptives and St. John¹s wort, an herbal supplement, may need to use back-up birth control methods. The herbal product can interact with several drugs including antiretrovirals, anticoagulants, digoxin, theophylline, and cyclosporine. It appears that St. John¹s wort may also decrease the effectiveness of oral contraceptive pills. Schweizerische Rundschau fur Medizin Praxis 2001;90:843-849.
Infectious Disease
Coinfection with HIV and heptitis C (HCV) is common with at least 33% of patients with HIV also having HCV. It appears that the damage that HCV causes to the liver occurs faster if HIV is also present. Detecting HCV may be difficult in patients with HIV due to low CD4 cell counts, but HCV RNA assays can detect viral replication. Maximizing therapy to improve the treatment of HIV is desirable, since low CD4 cell counts have been associated with greater liver fibrosis. Many drugs used to treat HIV can damage the liver so caution needs to used when using these drugs in patients with HCV infection. Interferon has been used to treat HCV. Long-acting interferons are now available and they may increase the sustained HCV response in HIV-HCV coinfection. AIDS Read 2002;12:19-26.
Medication Errors
Medication errors are the largest component of medical errors with an occurrence in 3-6.9% of hospital inpatients. Studies have shown that dispensing errors (wrong drug or incorrect strength, for example) account for a minority of medication errors. In a recent study, the impact of clinical pharmacy services and pharmacy staffing on medication errors in U.S. hospitals was assessed. Medication errors occurred in 5.22% of patients admitted to the 1,081 hospitals included in the study each year. The presence of a drug information service, pharmacist-provided adverse drug reaction management, pharmacist-provided drug protocol management, pharmacist participation on medical rounds, pharmacist-provided admission histories, and increased staffing of clinical pharmacists/occupied bed were factors associated with decreased medication errors/occupied bed/year. Pharmacotherapy 2002;22(2):134-147.
Neurology
Patients with Parkinson¹s disease on chronic dopaminergic therapy are at risk for the development of hallucinations. It appears that dopamine agonists like levodopa have a role in why hallucinations develop. In a study, patients who had hallucinations before dopamine agonist therapy or those who developed hallucinations while on therapy were likely to continue having hallucinations. There was no association of increased mortality and hallucinations. Additionally, there were no effects of age, duration of Parkinson¹s disease, gender, and medication dose on hallucination development. Neurology 2001;57:2078-2082.
Over-the-counter Products
Use of a multivitamin in patients over the age of 65 years is likely a good idea. In a review of previously published data, a daily multivitamin/mineral supplement providing a total daily dose of 20 mg zinc, selenium 100 mcg, and vitamin E 200 mg may improve immune function, vaccine responses and reduce the risk of developing an infection. However, there are many unanswered questions about the use of vitamins and minerals including the desired formulations and doses. Clin Infect Dis 2001;33:1892-1900.
An herbal product, Xiao-qing-long-tang (XQLT), may be useful to treat asthma. The drug was shown to reduce the narrowing of the airways and inflammatory changes in response to an allergen in animals. Herbal products are not regulated by the FDA. Thus, the efficacy and safety of the product does not have to be shown in order to have the product be sold in the U.S.. All patients with asthma should have access to a short-acting beta-2 agonist such as albuterol for emergency use. Allergy 2001;56:1164-1171.
Prescription Costs
The amount of money spent on prescription drugs rose by 17.3% in the year 2000. Twenty percent of consumers out of pocket expenses for health care were due to prescription drugs, which was the largest single component. It is thought that these figures are due to patients¹ demands for drug coverage in their health plans, more new drugs on the market, and direct-to-consumer advertising. The impact of paying for prescription drugs is greatest for patients without insurance coverage. Health Affairs 2002;21:1.
A recent survey found that 16.1% of the U.S. population was uninsured. However, even if you are insured, you will likely be paying more for prescription drugs. Both copayments and premiums are rising with an increase in the average copayments for brand-name and generic drugs of 18.5% and 12.1%, respectively. The average copayment for managed care groups increased 22% in 2000, while the average copayment for employer groups increased 11% from 1999 to 2000. Costs are increasing in part due to the aging population that uses more and costlier drugs, and to the development of new drugs. The average ingredient cost per prescription was 51% higher for new drugs than for all others in 2000. New drugs are not available in a generic form, which is usually less expensive. Drug Benefit Trends 2002;14:5-15, Drug Benefit Trends 2002;13:6.
Results from a study on reference pricing, a strategy for limiting prescription drug reimbursement within a drug class to a certain amount, indicate that choice of an ACE inhibitor based upon price does not adversely affect healthcare resource use or costs because of an inappropriate drug switch. The strategy saved a lot of money but is controversial because opposers feel that it encourages doctors to favor a drug based on price. Ongoing studies with other drug classes will provide additional information on the advantages and disadvantages of reference pricing. NEJM 2002;346:822-829 and 855-856.
Psychiatry
Paroxetine (Paxil®), fluoxetine (Prozac®), and sertraline (Zoloft®) were equally effective for treatment of depression in a recent study. The choice of an initial selective serotonin reuptake inhibitor at least among these three drugs may be reasonably based upon cost. An exception to this statement is for patients with features of both anxiety and depression. Fluoxetine is available generically, and may be the least expensive option. JAMA. 2001;286(23): 29472955. Increased use of drugs for depression and greater insurance coverage for these drugs was found in another report. JAMA 2002;287:203-209.
Results from a recent survey of parents and teachers in a county of North Carolina indicate that more children have a diagnosis of ADHD and are receiving treatment than previously thought. Of 6,099 children, more than 15% of boys and 5% of girls in grades 1 through 5 were reported to have a diagnosis of ADHD. Of the 607 children with an ADHD diagnosis, 434 were on a medication with 93% on a stimulant. Treatment rates are considered abnormally high if they exceed the prevalence estimate of 3% to 5%. Additional studies are needed to clarify the number of children with ADHD. Use of the DSM-IV is recommended to aid in diagnosis, especially since the definition has been expanded to include inattentive children. If medication is prescribed, follow-up of the child and regular interaction between the doctor, teachers and parents is advised. Am J Public Health 2002 92:231-234.
Certain patients with depression may benefit from more intensive antidepressant therapy and mental health treatment according to results of a recent study. Patients including elderly women, individuals with less formal education, those with neurotic traits and the medically ill are those that may benefit from more aggressive therapy. Stressors often associated with lower socioeconomic status such as a lower level of social support and feelings often associated with neuroticism may increase the difficulty in effectively treating depression. Patients with concomitant medical conditions may need physical therapy and pain management along with their antidepressant therapy. Mental Health Weekly 2002;12(8):3-4.
Rheumatology
The use of etanercept (Enbrel®) at a subcutaneous dose of 0.4 mg/kg given twice weekly appears to be effective over a 2-year period in patients with polyarticular course juvenile idiopathic arthritis (JIA). All patients improved with a mean decrease of 49% in the average swollen joint count, and a mean percentage decline of 94% in the average tender joint count and 48% in the average total joint count. Additionally, the duration of morning stiffness consistently decreased to less than 10 minutes. Etanercept was well tolerated, anemia improved, and some patients were able to stop or lower their dose of NSAIDs or corticosteroids. Ann Rheum Dis 2002;61:171-173.
Patients on antihypertensive therapy should carefully watch their blood pressure if started on a COX-2 inhibitor such as celecoxib (Celebrex®) or rofecoxib (Vioxx®). These drugs like nonselective COX-2 inhibitors (i.e., ibuprofen) interfere with renal prostaglandin synthesis and thus, may increase blood pressure. Patients with an allergy to sulfonamides should not take celecoxib. Patients with asthma, hives, or allergic reactions to aspirin or other NSAIDs should not take celecoxib or rofecoxib. Celecoxib inhibits an enzyme in the liver (CYP 2D6), which may result in increased levels of drugs such as some antidepressants, antifungals, antipsychotics, analgesics, and beta-blockers. Pharmacotherapy 2001;21(10):1223-1232.
Drugs in Development
Rheumatoid Arthritis
A new drug that inhibits tumor necrosis factor alpha (TNF-a) is in development by Pharmacia Corporation and Celltech Group. TNF-a is a protein released by immune cells that can cause joint inflammation and destruction. Results from a clinical trial showed that 400 mg of CDP870 subcutaneously every four weeks for 12 weeks resulted in 60% of patients having a 20% decrease in counts for both tender and swollen joints and a similar reduction in patient pain assessment, patient and physician disease activity score, inflammation markers in the blood, and physical function. The most common adverse events were headache, nausea, and infection.
Attention Deficit Hyperactivity Disorder (ADHD)
Atomoxetine is a potent inhibitor of the presynaptic norepinephrine transporter and is thought to work by blocking norepinephrine, which modulates systems that control attention and activity. In a study, children ages 8 to 18 years had a significant reduction in their core ADHD symptoms and had improvement in their social and family functioning with atomoxetine at a dosage of 1.2 mg/kg/day. If approved, atomoxetine will be the first nonstimulant treatment for ADHD. This may be significant, since many patients do not respond or cannot tolerate a stimulant drug. The drug is under review by the FDA and is being developed by Eli Lilly. Pediatrics 2001;108:E83.
Alcoholism
An NDA application has been filed for acamprosate, a drug to treat alcohol dependence. The drug is currently used in 40 countries under the name Campral, but the exact mechanism of action is unknown. The drug, if approved, would be used in conjunction with counseling and other behavioral therapy and would be marketed by Forest Laboratories. In a meta-analysis of data from 9 trials, an abstinence rate of 33% was achieved with the drug compared with a rate of 22% with placebo over a 12-month period. The primary adverse event was nausea. The only other drugs approved in the U.S. to treat alcohol dependence are disulfiram (Antabuse®) and naltrexone (ReVia®). Alcoholism & Drug Abuse Weekly 2001;13(41):6.
Chronic Obstructive Pulmonary Disease (COPD)
A new anticholinergic drug for the treatment of COPD is under development by Boehringer Ingelheim in the U.S.. The drug is tiotropium bromide (Spiriva) and it works as an anticholinergic. Tiotropium is used to open the airways in patients with COPD such as emphysema or chronic bronchitis. It is under investigation in the treatment of reversible airways obstruction such as asthma. Tiotropium is structurally related to ipratropium, but with a prolonged bronchodilator action. Tiotropium can be dosed once daily versus four times daily with ipratropium. It appears that the impact of a missed dose will be minimal with tiotropium, as lung function slowly returned to pretreatment values over 2-3 weeks after stopping the drug. In a 12-week comparative study with ipratropium (Atrovent®), greater lung function improvement and less rescue albuterol use was associated with tiotropium use. Tiotropium is being developed as a dry powder for inhalation. The drug appears to be well tolerated with dry mouth as the most common adverse effect. Expert Opinion on Investigational Drugs. 2001;10(4):733-740.
Hypertension and Heart Failure
New drugs that antagonize the endothelin (ET) system are in development. ET is a family of three endothelium-derived 21-amino acid peptides, ET-1, ET-2, and ET-3. The ET system is activated in hypertension and heart failure. Endothelin-1 has potent vasoconstrictor properties, prolongs pressor action, and stimulates sympathetic nervous system and cell proliferation. The first ET receptor subtype is ETAR, which is located primarily on vascular smooth muscle cells and mediates vasoconstriction and proliferation. The second receptor subtype is ETBR, which is largely on endothelial cells and mediates vasorelaxation and clearance of ET-1. Early clinical trials suggest that drugs that antagonize the ETAR and/or the ETBR are effective in the treatment of heart failure, essential hypertension, pulmonary hypertension, and atherosclerosis. Pharmacotherapy 2002;22:54-65.
Vasopeptidase inhibitors are a class of drugs in development that increase the actions of natriuretic peptide and suppress the renin-angiotensin-aldosterone system. These drugs work by inhibiting neutral endopeptidase and angiotensin-converting enzymes and may be effective for the treatment of high blood pressure and heart failure. One of these drugs in development is omapatrilat. Significant improvement in neurohormonal and hemodynamic status was noted in a study of patients with heart failure that received this drug. Additional studies are ongoing to determine the long-term safety and efficacy of these potential new drugs. Pharmacotherapy 2002;22:27-42.