UPDATES

By Carol A. Kemper, MD

Larium or Lamasil?

Source: Lobel HO, et al. JAMA 1998;280:1483.

This letter to the editor describes three cases of drug overdose with antimalarials, two of which resulted from dispensing errors for patients prescribed terbenafine (Lamasil) for onychomyosis. The first patient mistakenly received mefloquine 250 mg daily for three weeks, and then 2-3 times weekly for six months. He became increasingly weak, depressed, disoriented, and developed parathesias for three months before the error was discovered. He had not fully recovered one year later. The second patient similarly received mefloquine 250 mg daily instead of Lamasil. Within 10 days, she developed ataxia, confusion, speech impairment, and high-frequency hearing loss. She continued to receive the incorrect drug for a total of 61 days before the error was detected. Only hearing loss remained one year later.

The third case, which was much more frightening, involved a patient in a California hospital with Plasmodium vivax infection. She received 1250 mg of mefloquine on day 1, and 1260 mg of primaquine on day 2, at which time she became acutely jaundiced. She continued to receive primaquine 15 mg per day for five days. She developed acute hepatic necrosis, and was temporarily placed on the liver transplant list, but fortunately recovered.

In contrast to mefloquine, which has a high toxicity margin, primaquine has a fairly narrow margin of toxicity. The usual adult dose is 15-30 mg daily, but the probable lethal oral dose is 5-50 mg/kg (about 350-3500 mg for this patient). Not only does the treatment of malaria require expert knowledge (or advice), but these cases demonstrate why it’s better to write prescriptions using the generic name of drugs in most cases. We should all be aware of the potential for confusion of Larium and Lamasil.

Hepatitis A Vaccine in HIV-Infection

Source: Orenstein R, Stewart M. 36th IDSA, Denver, November 12-15, 1998; Abstract 411.

Orenstein and colleagues examined the cost-effectiveness of three strategies for administration of hepatitis A vaccine in HIV-infected patients. They based their calculations on the seroprevalence rates of their patients at the VA Medical Center in Richmond, Va., 25% of whom were HAV IgG seropositive, 43% were HCV seropositive, and 32% both. The cost of two doses of Hepatitis A vaccine was $50 and that of HAV serology was $10.

The most cost-effective strategy ($22.45 per pt.) involved vaccinating only those HCV seropositive patients who were also HAV negative. In contrast, screening for HAV IgG and vaccination of all seronegatives cost $57.25 per patient, and no screening and vaccination of all subjects cost $63 per pt.

The first approach is based on recent reports that acute HAV infection is more severe in patients with chronic liver disease due to HCV infection. However, this strategy does not account for the cost of HCV-screening, nor the cost of missed work, clinic visits, additional laboratory costs, and possible hospitalization, or the confusion generated by acute HAV infection in an HIV-infected individual receiving multiple, potentially hepatotoxic, medications.

The U.S. Public Health Service recommends Hepatitis A vaccination for individuals at risk for HAV infection. Not only are HIV-infected patients frequent travelers, but sexually active gay men are at risk for acute HAV infection. Hepatitis A vaccination should be offered to all HIV-infected individuals who are sexually active gay men, who work in the food or health care industry, travel to developing countries, or who have chronic liver disease, or chronic Hepatitis B or C infection—which, after examining the list, seems pretty inclusive.

Different Diet, Less Gas?

Source: King TS, et al. Lancet 1998;352:1187.

King and associates examined whether colonic malfermentation could be a factor in the pathogenesis of Irritable Bowel Syndrome (IBS). Six female IBS patients and six female controls were enrolled in a randomized, cross-over study in which subjects received either a standard diet (containing the usual Western foods) or an elimination diet for two weeks, followed by the alternate diet for two weeks after a two-week washout period. The elimination diet included fish and meat, but not beef, soy products replaced dairy products, and cereals other than rice were prohibited. There were also restrictions on yeast, citrus, caffeine, and tap water.

Toward the end of each two-week diet, fecal excretion of fat, nitrogen, starch, and non-starch polysaccharide was measured, along with a 24-hour indirect calorimetry.

On the standard diet, colonic gas production of hydrogen was two times higher in IBS patients than controls, and excretion of hydrogen plus methane was nearly four times higher. While both IBS and control subjects had reduced gas production, especially of hydrogen, while receiving the elimination diet, the IBS patients had near-normalization of their gas excretion patterns. This was associated with significant improvement in their gastrointestinal symptoms. King et al speculated that the elimination diet favorably alters the activity of certain bacteria, thereby decreasing symptoms of IBS.