Zanamivir and oseltamivir: two new options for the treatment and prevention of influenza.

BACKGROUND: Influenza infection is responsible for thousands of hospitalizations and deaths in the United States each year. Until recently, management options were limited to vaccination or use of the antiviral agents amantadine and rimantadine. Two antiviral drugs, zanamivir and oseltamivir, have recently been approved by the US Food and Drug Administration for the treatment of influenza A and influenza B. OBJECTIVE: This article reviews the published data on the pharmacology and clinical utility of zanamivir and oseltamivir in the treatment and prevention of influenza A and influenza B illness. METHODS: To identify relevant literature, a search of MEDLINE, International Pharmaceutical Abstracts, and the Iowa Drug Information Service was conducted for the period from 1969 to 2000. The search terms used were influenza, neuraminidase, zanamivir, oseltamivir; amantadine, and rimantadine. The reference lists of the articles so obtained were used to identify additional publications. RESULTS: Zanamivir and oseltamivir inactivate viral neuraminidase, an enzyme responsible for cleaving sialic acid residues on newly formed virions as they bud off from the host cell. This inhibition results in aggregation of virions on the surface of the host cell, which limits the extent of infection and speeds recovery from illness. Clinical studies have shown that neuraminidase inhibitors can decrease the median duration of influenza-related symptoms by approximately 1 day if initiated within 48 hours of the onset of symptoms of influenza. CONCLUSIONS: Evidence supports the use of zanamivir and oseltamivir in the treatment of influenza; however, additional studies are needed to clarify their utility and tolerability in pediatric and high-risk patients, as well as their utility in the prevention of influenza.

Impact of the development of a multidisciplinary adverse drug reaction committee.

A multidisciplinary Adverse Drug Reaction (ADR) committee consisting of pharmacists, nurses, and physician was formed. The committee developed an ADR Reporting Form and a 24-hour ADR Reporting Hotline to simplify ADR Reporting throughout the hospital. An ADR Newsletter and an extensive inservice education program was also implemented. Suspected ADRs are investigated by a pharmacist and presented to committee. A formal report is then forwarded to the Pharmacy and Therapeutics Committee, as well as the clinical departments within the hospital. The establishment of a formalized multidisciplinary ADR committee was successful in generating 2.1 ADR reports per 100 hospital admissions. These ADRs were reported from a variety of healthcare professionals.

Evaluation of effects of altered gastric pH on absorption of dapsone in healthy volunteers.

A prospective, randomized, crossover study was performed with seven healthy volunteers to address the effect of increased gastric pH on dapsone absorption. Subjects were randomized to receive a single 100-mg dose of dapsone or a single 100-mg dose of dapsone in addition to 30 ml of a high potency antacid 1 h before dapsone administration and hourly thereafter for a total of 10 doses. Dapsone concentrations in serum were measured periodically for 48 h. No statistical differences between the two regimens were noted when mean dapsone maximal initial concentrations, times to peak, and areas under the curve were compared. These data suggest that an increase in gastric pH has little or no effect on the absorption of dapsone in healthy subjects.

Endocrine complications associated with human immunodeficiency virus infection.

The causes and management of endocrine disorders associated with human immunodeficiency virus (HIV) infection are reviewed. Endocrine disorders observed in HIV-positive patients include adrenal abnormalities, hyporeninemic hypoaldosteronism, pituitary insufficiency, pancreatic abnormalities, thyroid and parathyroid disorders, and testicular abnormalities. Opportunistic pathogens implicated in these disorders include cytomegalovirus, Cryptococcus, Toxoplasma, mycobacteria, Candida, and Aspergillus. Neoplasma such as Kaposi's sarcoma and lymphoma can also cause endocrine abnormalities. Several drugs used in patients with the acquired immunodeficiency syndrome (AIDS) are associated with the development of endocrine disorders. These drugs include ketoconazole, itraconazole, rifampin, vidarabine, pentamidine, trimethoprim-sulfamethoxazole, didanosine, and ganciclovir. Severe patient debilitation can contribute to the development of endocrine abnormalities. Monitoring of adrenal gland function may be prudent in HIV-infected patients who have nonspecific symptoms of adrenal insufficiency. If adrenal insufficiency is diagnosed, replacement therapy with oral hydrocortisone is required. Administration of fludrocortisone can rapidly alleviate the signs and symptoms of hyporeninemic hypoaldosteronism. Fluid restriction is the first step in managing the pituitary abnormality known as the syndrome of inappropriate secretion of antidiuretic hormone. Drug-induced endocrine abnormalities often resolve after withdrawal of the offending agent. Endocrine complications in HIV-infected patients may be caused by infection, malignancy, or drugs. Adjusting or instituting drug therapy may be necessary to control symptomatic endocrine abnormalities.

Psychiatric disturbances associated with ganciclovir therapy.

OBJECTIVE: To report a case of possible ganciclovir-induced psychiatric disturbances. CASE SUMMARY: A patient with AIDS who had no known psychiatric history and mild renal dysfunction experienced exacerbation of cytomegalovirus retinitis and was treated with ganciclovir 5 mg/kg iv q12h. The patient complained of nightmares and developed visual hallucinations and severe agitation on day 15 of ganciclovir therapy. The problems resolved after haloperidol administration and ganciclovir withdrawal and reappeared when the same regimen was reinstituted. However, the patient was able to tolerate the maintenance dose of ganciclovir at 5 mg/kg/d along with haloperidol later without further episodes of visual hallucinations. DISCUSSION: Case reports in the literature on ganciclovir-or its analog, acyclovir-, induced psychiatric disturbances were reviewed and compared. The potential relationship between ganciclovir accumulation in patients with renal insufficiency and the observed central nervous system problems in our patient was postulated. CONCLUSIONS: It is likely that ganciclovir accumulation contributed to the acute psychotic episodes observed in our patient. Adjusting ganciclovir dosage based on the patient's renal function is probably the only approach required to prevent or reduce the incidence of these episodes.

Aseptic meningitis associated with naproxen.

A rare complication of nonsteroidal antiinflammatory drug (NSAID) use, particularly in patients with collagen vascular or autoimmune diseases, is aseptic meningitis. A healthy 21-year-old man receiving naproxen for muscle spasm was admitted with a chief complaint of severe headache. Approximately one week after beginning naproxen, the patient developed headache, fever (T 38.8 degrees C), shaking chills, and nuchal rigidity with occasional nausea and vomiting resulting in a 15-lb weight loss. Findings from a cerebrospinal fluid examination revealed polymorphonuclear pleocytosis and elevated protein, but no evidence of infection with bacteria, fungi, mycobacteria, or viral agents was noted. Within 36 hours of discontinuing naproxen, the meningitis-like symptoms markedly improved. Rechallenge with naproxen was not performed. In patients exhibiting meningitis-like symptoms, a thorough drug history, including that of recent or intermittent NSAID use, should be obtained.