Bruce H. Woolley, Pharm.D., Editor
Vol. 6, No.6
Kenneth J. Hunt, Associate Editor
NEW CLASS OF ANTIPLATELET AGENTS
A new class of antiplatelet agents has recently emerged that inhibit platelet glycoprotein IIb/IIIa. Abciximab is the first drug of this class to be introduced. Clinical trials on the drug have clearly demonstrated that the use of abciximab in combination with heparin and aspirin reduces the incidence of cardiac ischemia complications in the first month after coronary revascularization. The problem now facing physicians and patients is the drug's high cost of acquisition which may limit the widespread use of the drug.
It has been estimated that overall treatment costs over a six month treatment period were higher in abciximab patients than in a placebo group. This discrepancy was due to the high cost of the medication itself. However, patients treated with abciximab required fewer revascularization procedures during and after the six month treatment period. Thus, costs associated with hospitalization and procedures during a follow-up period were greatly reduced in patients receiving abciximab, and the money saved largely offsets the drug acquisition costs.
The deciding factor in this cost-effectiveness issue is the long term benefit of abciximab, which has not yet been confirmed in the literature. The first major clinical trial on the drug, known as EPIC (Evaluation of Platelet IIb/IIIa Antibody for Preventing Ischemic Complications of High Risk Angioplasty trial) demonstrated that abciximab has the potential to be cost effective. Data from the trial, however, do not accurately reflect how the drug will affect total treatment cost in clinical practice.
Before making a decision on the cost-effectiveness of this new class of drugs, it is important to recognize that we need more information. As new treatment protocols for bleeding complications continue to emerge, abciximab may not be the best of the current options. As this class of compounds continues to be studied and the pharmaceutical technology advanced, costs may be driven down and better treatments may develop. The impact on other health sectors and cost reduction possibilities must also be investigated.
Drug & Therapeutics Perspectives 13(5): 13-16, 1999
ADDERALL® MORE EFFECTIVE IN ADHD TREATMENT
In treating Attention Deficit and Hyperactive Disorder, an increasingly common problem in children and teenagers, the drug of choice has typically been methylphenidate (Ritalin®/Novartis). According to a recent study reported in Pediatrics, a newer compound, amphetamine sulfate (Adderall®/Richwood), produced behavior changes equivalent to those produced with methylphenidate at a lower dose. It also lasted two hours longer on average.
The head-to-head trial comparing the two drugs involved 25 children with ADHD who were enrolled in a summer daycamp as part of a double-blinded study. All subjects received a low or high dose of one of the medications or a placebo. The investigators found that several behaviors which are typical for ADHD patients such as attention and following rules were slightly improved even at lower doses (7.5 mg) of Adderall but only in higher doses (17.5 mg) of methylphenidate.
In addition, instructors and counselors evaluated classroom behavior and academic performance during the day and parents scored children's behavior each night. Both teachers and parents perceived improvements in the children's conduct for those on all doses of Adderall, but only on the higher doses of Ritalin. The staff at the daycamp recommended Adderall as the medication of choice for 52% of the children with ADHD that they dealt with. They recommended methylphenidate for only 12%.
Amphetamine sulfate was approved by the FDA in 1996 and has since sold more the 2.3 million prescriptions. Clinical trials demonstrate that the drug is at least as effective as methylphenidate and last up to two hours longer. It remains important that children receiving this or any drug of its type receive behavioral therapy so that they may eventually discontinue use of the drug.
Problems with compliance must also be addressed. Many children fail to take the daytime dose required while they are at school and many schools forbid personnel to administer the drug. Many teenagers also sell or give the drugs to friends. The choice between the two medications remains one of physician preference, however, a drug which lasts longer and is effective at lower doses is welcome in the treatment of ADHD.
Pediatrics (1999; 103:E43)
CANCER RISKS WITH CHRONIC HEARTBURN
For those who find themselves relying regularly on antacids and other drugs to control heartburn, there may be more to be concerned about besides controlling the uncomfortable symptoms. People who have frequent heartburn may be at a greatly increased risk for esophageal cancer.
Heartburn is the result of backward flow of stomach acids into the esophagus. It is relatively harmless when it occurs infrequently. For those with chronic heartburn, the cells of the esophagus, which are usually quite soft, must harden themselves to be protected from the frequent onslaught of acid from the stomach. This cell toughening is what is believed to predispose esophageal tissue to grow cancerous tumors.
In a recent Swedish study, researchers found that those who suffer from heartburn at least once a week are almost eight times more likely to develop esophageal cancer as those who get heartburn less frequently. People who get heartburn more frequently than once per week are at an even greater risk.
Cases of esophageal cancer are still quite rare in the United States, although they seem to be on the rise, especially in white males. The cancer is difficult to treat as it is rarely diagnosed in its early stages. Furthermore, the drugs sold to remedy the symptoms of heartburn do not delay the cellular changes which may lead to cancer. Patients with chronic heartburn should be put under close surveillance for complications and to detect a tumor as soon as it is apparent.
Thanks to Tufts Health and Nutrition Letter, Vol. 17, No. 3
SPOTLIGHT ON HERBS:
Milk Thistle For thousands of years, the seeds of the prickly leafed, purple-flowered plant Silybum marianum have been used to treat liver disorders. Parts of the plant have also been consumed historically as vegetables without report of toxic effects. The active component of the plant, silymarin, has been demonstrated in animal experiments to protect against a variety of hepatotoxic agents and processes in animal experiments. Evidence of its effects in humans is promising, but remains highly speculative and preliminary.
The best human data deal with silymarin's effect on cirrhosis of the liver and they have conflicting results. In the first of two RDBPC trials, the mortality rate for cirrhosis patients decreased by 30% in those treated for 2 years with 140 mg of silymarin 3 times a day. Effects were greatest in alcohol-related cirrhosis (1). In contrast, a recent multicenter RDBPC trial in two hundred patients with alcoholic cirrhosis found little to no differences in progression of disease or mortality after two years of treatment with 150 mg of silymarin three times per day. Many European physicians routinely treat hepatotoxic mushroom poisoning with intravenous silymarin at 20 to 50 mg/kg per day, decreasing mortality rates by more than half in several case series.
In animal studies, silymarin protects liver cells against a variety of hepatotoxins, including the drugs acetaminophen, amitriptyline, and erythromycin. It is also purported to protect against certain toxins, including amantin from deathcap mushrooms, alcohol, and carbon tetrachloride. Silymarin scavenges free radicals, blocks toxin entry into cells by competing for receptor sites, inhibits inflammation, and stimulates liver regeneration (2).
The use of milk thistle should undergo further investigation as a hepatoprotective agent before concrete conclusions can be made. No adverse effects have been reported, so there is little to fear for those currently using the agent. Diabetic patients taking silymarin should carefully monitor their blood glucose to avoid hypoglycemia. The common dose of milk thistle is a 140-mg capsule, standardized to 70% silymarin, 2 to 3 times a day. A high first-pass effect concentrates silymarin in the liver. As silymarin is poorly absorbed, concentrated extracts are ideal.
1. Pares A, Planas R, Torres M, et al. Effects of Silymarin
in alcoholic cirrhosis of the liver: results of a controlled, double-blind,
randomized and multicenter trial. J Hepatol. 1998;28:615-621.
2. Lawrence Review of Natural Products. Milk Thistle. St Louis, Mo: Facts and Comparisons; 1994.
A new popular dietary supplement called SAM-e (S-adenosyl-L-methionine) is being touted for the treatment of depression and for relief of osteoarthritis. This compound is an endogenous compound produced from methionine. It is involved the biosynthesis of certain neurotransmitters and phospholipids, as well as proteins. Clinical use in Europe has shown effectiveness in mood enhancement and potential cartilage synthesis and repair. Side effects are most often associated with the gastrointestinal system and include nausea and vomiting. In addition, large doses can cause anxiety.
A daily multivitamin called Cernevit–12 (Baxter) was approved for parenteral or intravenous use in patients 11 years of age and older. The mixture contains RDA levels or higher of alpha–tocopherol, ascorbic acid, biotin, cholecalciferol, cyanocobalamine, folic acid, niacin, pantothenic acid, pyridoxine, riboflavin, thiamin, and vitamin A.
An approvable letter has been received for rivastigmine (Exelon®/Novartis) for the treatment of Alzheimer's disease. The clinical trials involved 3,7000 patients with the disease. Side effects included nausea, vomiting, painful digestion, loss of energy, and anorexia.
Paroxetine (Paxil®/SmithKline Beecham) has received approval for the treatment of social anxiety disorder. On a clinical study 69% of patients improved their functioning in social settings as compared to 29% for those receiving a placebo. Paroxetine is already approved for the treatment of depression, obsessive compulsive disorder, and panic disorder.
An FDA committee has voted unanimously NOT to recommend tirilazad (Freedox®/Pharmacia & Upjohn) for approval. The committee felt that there is not enough evidence to support efficacy for the treatment of aneurysmal subarachnoid hemorrhage.
The FDA has asked Searle to consider changing the name of celecoxib (Celebrex®) because of potential confusion with the SSRI citalopram (Celexa®)and the anticonvulsant fosphenytoin (Cerebyx®). The company has already changed the name once before marketing to avoid confusion.
In a study of 50 obese women, bupropion (Glaxo-Wellcome) was shown to be an effective anti-obesity therapy. Sixty-seven (67%) percent of these women lost more than 5% of their body weight after treatment and a 1,600 calorie diet. Only 15% matching participants who received a placebo had the same weight loss. The women treated with bupropion lost an average of 13.7 pounds as compared with 3.4 pounds for those taking placebo
A new test to quickly diagnose the presence of influenza A or B virus (Zstat®/ZymeTx) has been shown to save money and reduce the time patients spend in the physician's office or in the emergency room. The test, which reduces the number of laboratory tests and chest x-rays used to rule out bacterial infections, is effective in children presenting with flul-like symptoms.
The information and opinions expressed in the Therapeutics Letter do not necessarily reflect the official policy of the sponsoring organizations.