Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ganciclovir is a congener of acyclovir with in vitro activity against cytomegalovirus. Ninety-seven patients with the acquired immune deficiency syndrome (AIDS) and a serious cytomegalovirus infection received ganciclovir, 3.0 to 15 mg/kg per day. Viremia cleared during drug therapy in 88 percent of patients. Viral shedding from urine and throat ceased or became inapparent during treatment in 78 percent and 68 percent of patients, respectively. Among patients with cytomegalovirus retinitis, 87 percent of evaluable patients had improvement in (30 of 60) or stabilization (22 of 60) of their disease. However, when the drug was discontinued, progression or recurrence of disease always occurred. Long-term suppressive therapy with ganciclovir, 5.0 mg/kg five to seven times weekly, prevented the recurrence of cytomegalovirus disease (p less than 0.001). The drug was eliminated by renal excretion, and in patients without renal impairment (creatinine clearance rates of more than 60 ml/minute/1.73 m2), ganciclovir has a mean half-life of 4.2 hours. Significant neutropenia and leukopenia occurred in 55 percent and 32 percent of patients, respectively.
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PMID:Ganciclovir for the treatment and suppression of serious infections caused by cytomegalovirus. 303 41

The antiviral nucleoside analogue ganciclovir has demonstrated in vitro activity against human cytomegalovirus and effectively treats infection caused by this organism in various immunocompromised patient groups. The drug prolongs time to progression in patients with acquired immune deficiency syndrome (AIDS)-related cytomegalovirus retinitis although life-long maintenance therapy is required. Direct comparisons between ganciclovir and foscarnet in this indication are few; nevertheless, the 2 drugs appear to have equal therapeutic efficacy in treating cytomegalovirus retinitis although results from 1 study in this indication suggest that foscarnet has an advantage in terms of patient survival. AIDS-related gastrointestinal and, to a lesser extent, pulmonary cytomegalovirus infection also respond to treatment with ganciclovir; maintenance therapy does not appear to be required in these latter 2 indications. Ganciclovir is also useful against cytomegalovirus infection in organ transplant recipients. The drug is most effective when given prophylactically or as early treatment for asymptomatic infection in bone marrow transplant recipients; treatment of established infection is less effective in this patient group. However, established infection in solid organ transplant recipients appears to respond to treatment with ganciclovir. The most common adverse event during ganciclovir therapy is haematological toxicity but this appears to be readily reversible on discontinuation of the drug. In addition, coadministration of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF) has been shown to prevent ganciclovir-associated neutropenia. Thus, ganciclovir is a valuable treatment for cytomegalovirus infection in patients with AIDS and in organ transplant recipients. Further studies comparing ganciclovir and foscarnet-ideally incorporating the use of G-CSF or GM-CSF to prevent ganciclovir-associated neutropenia and assessing survival as 1 endpoint--should further clarify the relative role of ganciclovir as treatment or prophylaxis for cytomegalovirus infection.
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PMID:Ganciclovir. An update of its therapeutic use in cytomegalovirus infection. 752 63

The efficacy and safety of a combination of ganciclovir plus GM-CSF was evaluated in AIDS patients with cytomegalovirus retinitis. In phase A, patients were randomized to receive ganciclovir, 5 mg/kg every 12 h for 14 days followed by 5 mg/kg daily, with (n = 24) or without (n = 29) GM-CSF (1-8 micrograms/kg daily subcutaneously) to maintain absolute neutrophil counts between 2500 and 5000 cells/microliters. In phase B, after 16 weeks zidovudine was added to the regimen of 16 patients receiving ganciclovir plus GM-CSF and 20 receiving ganciclovir alone. At this stage, GM-CSF was added to the treatment protocol of any patient receiving ganciclovir plus zidovudine who became neutropenic. In phase A, patients in the ganciclovir plus GM-CSF group had significantly higher neutrophil counts than ganciclovir-alone patients (p = 0.0001). Overall, 12.5% of patients treated with GM-CSF developed neutropenia (absolute neutrophil counts < 500/microliters phase A and < 750/microliters phase B) compared with 45% of patients treated without GM-CSF. GM-CSF patients missed 10 of a possible 4705 scheduled doses of ganciclovir compared with 34 missed doses of a possible 6584 in the ganciclovir-alone group (p = 0.011). There was a trend, although not statistically significant, for patients in the GM-CSF group to experience delayed progression of their retinitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. The ACTG 073 Team. 787 51

AIDS patients with newly diagnosed cytomegalovirus (CMV) retinitis who had just completed a 14-day course of ganciclovir induction therapy were randomly assigned to an alternating or concurrent combination regimen of chronic ganciclovir-foscarnet therapy for CMV retinitis. Each regimen used lower weekly cumulative doses of each drug than standard monotherapy maintenance treatment regimens. Dose-limiting toxicity attributable to foscarnet occurred in only 2 (7%) of 29 evaluatable patients, and no patients experienced dose-limiting nephrotoxicity. Although absolute neutrophil counts < 500 cells/microL occurred in 11 (38%) of 29 patients, all who subsequently used adjunctive granulocyte colony-stimulating factor had severe neutropenia prevented. Severe toxicity of any type and neutropenia, in particular, occurred significantly more frequently in patients assigned to the concurrent treatment regimen. CMV was isolated from none of 21 patients who had urine cultured and from only 1 of 24 who had blood cultured while being treated during the study (median evaluation, 12 weeks). This suggests that combination therapy provides better in vivo antiviral activity in suppressing CMV replication than previously reported with monotherapy regimens.
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PMID:Randomized phase I trial of two different combination foscarnet and ganciclovir chronic maintenance therapy regimens for AIDS patients with cytomegalovirus retinitis: AIDS clinical Trials Group Protocol 151. 801 96

A 41-year-old man with acquired immunodeficiency syndrome (AIDS) developed cytomegalovirus (CMV) retinitis. Intravenous administration of ganciclovir arrested progression of the retinitis, but it was discontinued due to side effects of severe anemia, neutropenia, and thrombocytopenia. Reactivation of CMV retinitis occurred two weeks after stopping ganciclovir, and then forscarnet was given intravenously. The response was prompt with resolution of the retinitis. There was no progression of retinitis during the treatment. The patient experienced renal dysfunction as a side effect of foscarnet, but it was reversible. As with ganciclovir, foscarnet appeared to be an effective drug for CMV retinitis associated with AIDS. Both drugs have severe adverse events: foscarnet causes renal dysfunction and ganciclovir causes myelosuppression, that necessitated discontinuation of the therapy. We suggest that alternating ganciclovir and foscarnet administration, switching to other treatment on the basis of the clinical response and side effects of the drugs, is an efficacious regimen for the treatment of CMV retinitis associated with AIDS.
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PMID:[Foscarnet for cytomegalovirus retinitis in a patient with acquired immunodeficiency syndrome]. 806 6

Cytomegalovirus retinitis, an opportunistic infection caused by the herpesvirus cytomegalovirus, is a major cause of illness in patients with advanced AIDS. As infected patients require long term drug treatment to delay disease progression and minimise loss of vision, the disease is associated with substantial treatment costs which considerably increase overall expenditure on AIDS-related health care. During the last decade, intravenous ganciclovir has been a mainstay of treatment for patients with cytomegalovirus retinitis. However, notwithstanding its demonstrated efficacy as maintenance therapy for this condition, long term intravenous drug administration is both inconvenient and uncomfortable for many patients. Moreover, neutropenia and catheter-related infections have been reported commonly in patients receiving ganciclovir via the intravenous route. To overcome the limitations of intravenous ganciclovir, an oral formulation of the drug has been developed for use as maintenance therapy. In comparative clinical trials, both intravenous and oral ganciclovir maintenance therapy slowed disease progression and preserved visual acuity in patients with stabilised cytomegalo-virus retinitis, although there was evidence that the intravenous formulation was more effective in terms of delaying recurrence of active disease. This suggests that oral ganciclovir use should be limited to the treatment of patients without evidence of immediately sight-threatening cytomegalovirus retinitis. Three published cost analyses, which were based on efficacy and tolerability data derived from 2 randomised, comparative clinical trials, have shown that oral ganciclovir maintenance therapy offers cost advantages over intravenous maintenance therapy, despite the higher acquisition cost of the oral formulation. The higher overall costs of intravenous maintenance treatment, compared with oral therapy, were attributed to higher drug administration and adverse event treatment costs. In one analysis, estimated lifetime treatment costs of oral maintenance therapy were 25.2% lower than those of intravenous maintenance treatment. As yet, no formal cost-effectiveness evaluations of oral and intravenous ganciclovir have been published. Few published data are available regarding the relative effects of intravenous and oral ganciclovir on quality of life. However, in a health state utility analysis, there was a large overall preference among HIV-infected individuals for oral over intravenous maintenance treatment. In conclusion, oral ganciclovir appears to be a cost-saving and patient-preferred alternative to its intravenous counterpart for the maintenance therapy of AIDS patients with stabilised cytomegalovirus retinitis in whom there is no evidence of sight-threatening disease.
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PMID:Ganciclovir. A pharmacoeconomic review of its use as intravenous or oral maintenance therapy in the management of cytomegalovirus retinitis in patients with AIDS. 1016 72

According to Gilead, the maker of cidofovir (formerly called HPMPC), early trial results show a promising level of effectiveness in delaying the progression of cytomegalovirus (CMV) retinitis in people with AIDS. The study compared immediate versus deferred treatment with the antiviral drug for CMV retinitis in people with AIDS. CMV progressed in an average of 22 days for the group that delayed treatment, versus 120 days for the group receiving cidofovir. Cidofovir, under the brand name Vistide, is administered by intravenous infusion once a week for two weeks, and then twice monthly. Side effects include proteinuria, neutropenia, and peripheral neuropathy. Cidofovir is available through an open-label expanded access program.
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PMID:Cidofovir (HPMPC) potent against CMV. 1136 67

Oral ganciclovir is the only approved pill treatment for cytomegalovirus (CMV) retinitis. However, it is poorly absorbed by the body, so patients may need to take 12 pills a day for it to be effective. A clinical trial will compare the new version, ganciclovir prodrug (RS-79070), to oral ganciclovir for CMV retinitis. Possible side effects include neutropenia, anemia, diarrhea, and nausea. Study details and contact telephone numbers are provided.
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PMID:Pill treatment for CMV. 1136 19

Ganciclovir eye implants have conclusively been shown to be more effective than intravenous (IV) ganciclovir in preventing progression to CMV retinitis. In a randomized trial, median time to progression was 221 days with the implant vs. 75 days with IV ganciclovir. Implants have become the standard of care although they have several disadvantages: they protect only one eye, they need regular replacement, they may lead to retinal detachment in some cases, and they cost up to $30,000 per year. Some doctors have put patients on oral ganciclovir after implant surgery to protect the other eye, however, it is not an ideal solution because it requires as many as 18 pills daily, causes neutropenia, is difficult to take with AZT, and costs up to $20,000 per year. CMV disease develops in 25 to 45 percent of AIDS patients. There are some early indications that the use of protease inhibitors may help heal retinal lesions in some patients. The U.S. Public Health Service has not changed the therapy guidelines for CMV prophylaxis.
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PMID:Eye implants shown superior to IV for retinitis. 1136 17

A home intravenous drug therapy provider and an insurance company operated by the American Consulting Engineers Council have gone to court over disputed medical claims. An AIDS patient being treated with ganciclovir for CMV retinitis had a decrease in his white blood cell count, neutropenia, that endangered his life. The physicians prescribed neupogen, approved by the Food and Drug Administration (FDA) for cancer treatment, to counteract the neutropenia. The health care provider, I.V. Services of America, continued the neupogen treatment; the treatments were covered as an inpatient but denied after discharge. I.V. Services sued, alleging that the cause of the neutropenia should not bar coverage. The New York judge found in favor of the health care provider, calling the insurance company's position self serving and the denial of the claim arbitrary.
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PMID:Court finds ambiguity in denial of off-label AIDS drug. 1136 66


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