|June 1998||Bruce H. Woolley, Pharm.D., Editor||Vol. 5, No.6|
NEW DRUG APPROVALS
The FDA has given approvable status to orlistattetrahydrolipstatin (Xenical®/Roche). The non-systemic acting antiobesitymedication inhibits approximately 30 % of ingested fat through blocking lipase in the G.I.tract. The FDA has based final approval on the submission of safety data from clinicalprograms and final labeling. The requested additional information from the company isexpected to delay the availibility of the drug until early 1999.
rhIGF-1 (Myotripin®Chiron and Cephalon), a recomninant growth factor protein,is approvable for the treatment of amyotrophic lateral sclerosis [Lou Gehrig's Disease].Last year a FDA advisory committee recommended against approval after two clinical trialsdemonstrated conflicting results. The companies reevaluated the data and subsequentlysubmitted a different analysis of the same data.
The FDA has granted marketing approval for basiliximab (Simulect®/Novartis)for the prevention of acute rejection episodes in kidney transplant patients. The compoundis a monoclonal antibody that is administered in two doses. The first dose is given withcyclosporine and corticosteroids on the day of transplant with a second dose of the drugson the fourt day. Clinical trials demonstrated a one-third reduction in acute rejection.
Approvable status has been granted for citalopram (Celxa®/Forest), a selectiveserotonin reuptake inhibitor, for the treatment of depression. It will be co-marketed byForest and Warner-Lambert.
Marketing approval has been granted for tirofiban (Aggrastat®/Merck) fortreatment of patients with unstable angina. The drug is the first of a new class known asglycoprotein Iib/IIIa inhibitors [platelet blockers]. In one clinical trial the compounddemonstrated a 32% reduction in the risk of death, new heart attack or refractory ischemiawhen administered with heparin and aspirin as compared with heparin and aspirin alone. Themost common side effect was bleeding when administered in the above combination.
The FDA has granted marketing approval for the first oral micronized progesteronecapsules (Prometrium®/Solvay) for treatment of Secondary amenorrhea. Side effectsinclude abdominal cramping, headache, dizziness, and breast pain.
Eptifibatide (Integrilin®/Schering-Plough) has been approved for marketing as atreatment of acute coronary syndrome. It is approved for administration in the treatmentof patients undergoing percutaneous coronary intervention who do not present with a acutecoronary syndrome. It will be co-marketed in the United State by Schering-Plough and CORTherapeutics.
RECOMMENDED FOR APPROVAL
The Antiviral Drugs Advisory Committee of the FDA has recommended approval ofrifapentine (Prifun®/Hoechst-Marion Roussel) for the treatment of pulmonarytuberculosis when used in combination with at least one other anti-tuberculosis drug. Thelabeling probably will warn against the use of the drug in HIV-infected patients.
Two agents have been recommended as combination therapy for chronic hepatitis Cpatients 18 years of age and older who have relapsed after initial response to alphainterferon. The two agents are alpha interferon (Intron A®/Schering-Plough) andribavirin (Virazole®/ICN). The approval was based on two trials with a total of1,744 patients. One trial of 345 subjects demonstrated that 48.6% of patients showed notraces of hepatitis C vs. 4.7% who were given alpha interferon alone. Side effects weresimilar to those of alpha interferon and include headache, fatigue, and myalgia.
CHOLESTIN REMOVED FROM MARKET
The FDA has removed Cholestin® (Pharmex) from the market. In their ruling, theagency stated that the product is not a dietary supplement. They ruled that it is anunapproved drug that contained a substance that equates with lovastatin (Mevacor®/Merck),a cholesterol-lowering agent.
DECREASED RISK OF BREAST CANCER
On may 18th, data were presented to the national meeting of the American Society forClinical Oncology demonstrating a decreased breast cancer risk with tamoxifen (Nolvadex®/Zeneca)and raloxifene (Evista®/Lilly). Dr. Larry Norton of Memorial Sloan-KetteringCancer Center stated: "I foresee a day in the near future when all postmenopausalwomen, and some premenopausal women, will be taking something to prevent breastcancer."
In one study of 13,000 women in the National Surgical Breast and Bowel Project (NSBBP),Dr. Donald Wickerham reported a reduction in breast cancer risk by 45% over four years inwomen at higher risk of the disease, based on age, family history, delayed childbearingand other factors. However, tamoxifen, demonstrated a two to three-fold increase in therisk of uterine cancer, particularly for women over 50. In this study, 85 women takingtamoxifen developed breast cancer, vs. 154 women taking a placebo. Thirty-five womendeveloped uterine cancer, vs. 14 on placebo.
In a 2 1/2 year study of 7,705 post-menopausal women taking raloxifene to prevent boneloss, Dr. Steve Cummings of the University of California at San Fransisco reported areduction in the risk of breast cancer by about 70%. The participants in the study alsosaw a decrease in the risk of uterine cancer by about half, although this finding ispreliminary. Definitive studies concerning the decreased risk of uterine cancer areexpected to begin this fall.
BONE DENSITY TESTING
Bone consists of an organic matrix that is primarily collagen fibers in which aredeposited salts of calcium and phosphate in crystals of hydroxyapatite. The tensilecapacity of collagen and the compressional ability of calcium salts combine to give boneits density and strength. Peak bone mass is reached around the age of 25-33 years of ageeven though the long bones cease growing in length around age 20. The less dense the bone,generally, the greater the chance of developing osteopenis and/or osteoporosis later inlife.
Bone density testing is becoming more popular and as new devices are marketed, field isvery confusing. Some experts in women's health anticipate that bone density testing mayeven become part of the annual physical examination. these peripheral testing methodsgenerally use x-ray absorptiometry methodologies to determine measurements. However, it isimportant to understand what is actually being measured. Bone mineral density (BMD) ismeasured in mg/cc2 and is a measurement of mineral content by area. Bonemineral density is in mg/cc3 and is a measurement of mineral volume [density].Some devices report BMC but have actually measured BMD (and vice versa).
In one study conducted on 124 women at the University of California at San Fancisco, itwas estimated that 20% to 30% of women with low bone density at the spine or hip may bemissed with peripheral testing. However, that means that these tests will potentiallycatch between 70% to 80% with low bone mass and potential development of osteoporosis.
Some of the current bone density methodologies are listed in the following table:
|Name of Test||Sites Measured||Comments|
|DEXA (dual energy x-ray
|spine, hip, forearm||The gold standard method|
|p-DEXA||forearm||Os calis (heel may prove to be
the best peripheral site
|accuDEXA||middle finger||Inexpensive, may become most
available method, data not
|spine||Radiation dose is high, expensive
not readily available
|middle three fingers||Data not conclusive, may take two-to-
three weeks for results
instantaneous x-ray imager)
|heel, forearm||Os calis (heel) may prove to be the
best peripheral site
|US (ultrasound)||heel||Recently approved by FDA, first
without using radiation
The body cannot manufacture calcium and so all calcium must be ingested, either fromfood or by supplementation. In order to prevent a negative calclium balance, most adultsmust ingest at least 800 mg of calcium daily, which is less than the RDA. However, manyexperts suggest that a great proportion of the adult population do not even consume the800 mg. Although the best source of calcium is found in food, many times the healthprofessional may recommend a calcium supplement that will provide enough elemental calciumto prevent a negative balance. There are eleven common commercially available calciumsalts and hundreds of different preparations that are available in the United States.
Numerous factors should be considered when selecting a calcium preparation. Some ofthese factors include: physical properties (i.e., solubility, pH, interactions withconcomitant foods and drugs, dosage and timing, and bioabailability), pathophysiologicalconditions (i.e., lactose intolerance, impaired gastric acid secretion, and propensity forthe formation of stones).
|Salt||Brand Names||%ele Ca++||Amt ele Ca++ in
500 mg tab
|40||200 mg||39 (+/-)3|
|J. Bone Min Res 1988; 3(3):253-258||Calcif Tissue Int 1990; 46:300-304|
Although there are many different calcium salts available, only the carbonate, citrateand phosphate compounds have widely studied with regard to absorption and efficacy inpreventing bone loss and osteoporotic fractures. Generally, these are the three salts thatare most frequently recommended to the patient.
The information and opinions expressed in the Therapeutics Letter do not necessarilyreflect the official policy of the sponsoring organizations.