The Latest Information on New Drugs and New Indications
By William T. Elliott, MD, FACP
The FDA has approved a new drug for intermittent claudication. Cilostazol (Pletal-Otsuka America Pharmaceutical) is an inhibitor of platelet aggregation and a peripheral vasodilator. The drug also has a beneficial effect on lipid profiles. In seven placebo-controlled trials provided to the FDA, the drug resulted in improved absolute claudication distance and initial claudication distance—both measures of pain performed on a treadmill. Improvement was seen often within 2-4 weeks of initiating therapy. The drug is a phosphodiesterase III inhibitor, a class of drugs known to decrease survival in patients with severe CHF, and is, therefore, contraindicated in patients with CHF.
Strep pharyngitis in children may be effectively treated with a once-daily dose of amoxicillin according to a recent study (Pediatrics 1999;103:47-51). A single daily dose of 750 mg of amoxicillin was compared to penicillin V 250 mg tid, both given for 10 days. Cure rates were at least as good with amoxicillin as with penicillin, and both therapies were well tolerated.
There is something new to try for nocturnal leg cramps—a Taiwanese group is reporting that vitamin B complex was effective in more than 85% of patients with this difficult management problem (J Clin Pharmacol 1998;38:1151-1154). In a placebo-controlled study of 28 patients, three months of B-complex vitamins proved to be remarkably effective. Patients who were on medications known to cause nocturnal leg cramps, such as diuretics and calcium channel blockers, were excluded from the study.
Researchers from Johns Hopkins are reporting a setback to the development of an HIV vaccine (J Virol 1999;73:152-160). In India, the country facing the largest burden of HIV worldwide, HIV-1 subtype C is the most common variant. Subtype B has been the subject of most vaccine work to date worldwide. The researchers were able to sequence the genome of the C virus for the first time and found that the genes coding for the viral envelope differed significantly between the two viruses, implying that efforts to develop a vaccine to the B subtype may be ineffectual against subtype C. They also found a mosaic of subtypes A and C, a type of HIV that is common in Thailand and Brazil, unlike the United States where single-subtype strains are most common.
Searle’s celecoxib (Celebrex) has barely been approved for one month for the treatment of rheumatoid and osteoarthritis. Now, the company is evaluating whether the drug may help inhibit the progression of Alzheimer’s disease and whether it may help prevent colon cancer. The Alzheimer’s program is in Phase II, while the colon cancer prevention program is in Phase III.
Revaccination with the pneumococcal polysaccharide vaccine (PPV) has been considered somewhat risky because of the potential for severe local injection site reactions. A recent study from the University of Washington and the CDC has helped define the risk of revaccination (JAMA 1999;281:243-248). In more than 500 patients who were revaccinated, compared to more than 900 newly vaccinated individuals, there was a greater likelihood of local reactions, but the reactions were self-limited and did not represent a contraindication to revaccination. The researchers support the policy of a one-time revaccination at least five years after the initial vaccination with PPV for those 65 and older who were vaccinated before age 65, or those 64 and younger who are immunocompromised.
The FDA has approved SmithKline Beecham’s Lymerix, the first vaccine for the prevention of Lyme disease (see full review in the March issue). The vaccine is indicated for adults who spend leisure time or work outdoors in endemic areas such as the Northeast and upper Midwest. It is a unique vaccine, since the antibodies produced by the human host must be picked up by the tick, where they prevent transmission of the spirochete. The vaccine is given in three shots at 0, 1, and 12 months. Protection is only about 50% after the second dose, and 80% after the third dose, so other methods of protection, such as repellents, should be continued. The company is also investigating accelerated dosing regimens, injections at 0, 1, and 6 months and even 0, 1, and 2 months that seem to be as effective as the longer schedule. To get protection for this year’s tick season, the vaccine should be started soon.
For the technologically inclined, there is a new website that contains evidence-based clinical practice guidelines for clinicians. The National Guidelines Clearinghouse (NGC) is operated by the U.S. Department of Health and Human Services, Agency for Health Care Policy and Research (AHCPR) in partnership with the American Medical Association (AMA), and the American Association of Health Plans (AAHP). This is a remarkable site, with a wide wealth of information from leading policy setting groups. The site has a simple search engine and is easily accessible at www.guideline.gov.
The FDA was busy in 1998. The agency took action on 199 new drug applications and approved 90 of them. The time to approval is getting shorter, with the average being 12 months in 1998 compared to 14.4 months a year earlier. Twenty-five drugs with "potentially exceptional public health value" were given priority review status and received approval in just over six months. Several important drugs have recently joined the generic ranks as well. Generic versions of cyclosprorin, terazocin (Hytrin), tretinoin cream (Retin-A), and Dilantin Kapseals were all recently approved. In related news, Eli Lilly is in court trying to maintain its patent of fluoxetine (Prozac), which is scheduled to expire in two years. The company is fighting challenges from generic makers Barr, Geneva, Goldline, and Teva.
A new surgical sealant is being tested at Massachusetts General and other hospitals. The sealant is being used in thoracic surgery cases to stop air leaks. Focal’s FocalSeal-L surgical sealant was "very effective" in sealing air leaks during and after lung surgery. According to preliminary results of a multicenter study, 45% of patients treated with Focal Seal remained leak-free post-op through hospital discharge compared with 15% of patients in a control group. FocalSeal-L comes in a liquid form that is brushed onto the leak site and then photoactivated, which causes it to polymerize into a gel that is adherent, transparent, and elastic.
Good news for long-term users of NSAIDs. A recent study confirms their protective role against colon cancer (Arch Intern Med 1999;159:161-166). Use of these drugs on a regular basis, regardless of dose or type of NSAID, cut the risk of colon cancer in the elderly by as much as 50%. The protection was most pronounced for right-sided lesions and there was little effect on preventing rectal cancers.