A Comparison of the Effectiveness of Three Regimens in the Prevention of Pneumocystis carinii Pneumonia in Human Immunodeficiency Virus-Infected Patients

Martin, Mike; Cox, Patricia; Beck, Keith; Styer, Cathryn M.; Beall, Gildon N.

doi:10.1001/archinte.1992.00400150053009

Cited by 49 publications

(9 citation statements)

References 19 publications

(4 reference statements)

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“…Different rates of efficacy and safety have been reported, but some of these discrepancies can be attributed to type of prophylaxis (primary versus secondary), administration schedule and concomitant pyrimethamine prophylaxis or antiviral treatment with ddI [ 1 1,191. Once-daily administration of 50 to 100 mg of dapsone is poorly tolerated, with overall side effects ranging from 46% to 75% of patients, although highly effective (failure rates 2.1-6.4%) [10,20,24,26]. O n the other hand, once-weekly administration of dapsone is better tolerated, with side effects ranging from 2.3% to 11%, but less effective (failure rate 8.3-15.2%) [ 22,23,25].…”

Section: Discussionmentioning

confidence: 99%

Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data

Cruciani

Minelli

Mirandola

et al. 1996

Clinical Microbiology and Infection

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OBJECTIVES: In this study we evaluated the pharmacokinetics, efficacy and safety of dapsone given 100 mg twice weekly as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with HIV-1 infection. METHODS: This was a prospective open trial, evaluating a total of 55 HIV-1-infected patients with CD4 cell counts below 200/mm3 and without previous episodes of PCP. Plasma concentrations of dapsone were determined with high-performance liquid chromatography (HPLC). After a mean follow-up of 471 days, the PCP rates per year of observation were 6.79%. Discontinuation of treatment as a result of severe side effects was required in four patients (7.5%). At steady state, mean plasma concentrations 24, 72, 96 and 144 h following the administration of dapsone were 1.46plus minus0.8, 0.28plus minus0.20, 0.30plus minus0.21 and 0.37plus minus0.27 mg/L, respectively. Dapsone plasma levels showed a high interpatient variability. The values for the pharmacokinetic parameters were comparable to those described for healthy volunteers. CONCLUSIONS: The administration of 100 mg twice weekly of dapsone seems appropriate to maintain effective plasma concentrations of the drug and to prevent PCP with good safety in patients with HIV-1-related immunodeficiency.

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Section: Discussionmentioning

confidence: 99%

Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data

Cruciani

Minelli

Mirandola

et al. 1996

Clinical Microbiology and Infection

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“…The experience with dapsone as an agent for PCP prophylaxis in HIV-infected patients has been increasing over recent years. Dapsone has been tested as an agent for PCP prophylaxis at different dosage regimens, namely, 50 to 100 mg daily (4,16,18,22), 100 mg twice or thrice weekly (6,7,29,31), and 100, 200, or 300 mg once weekly (1,11,17,21,25,27). Even though the comparability of these investigations is hindered by such variables as disease stage at study entry, duration of follow-up, concomitant anti-HIV therapy, primary versus secondary prophylaxis, and risk factor, it appears that a daily dosage may be more effective but may be associated with higher rates of adverse reactions than weekly dosage regimens, while weekly regimens may be associated with lower rates of adverse effects and a higher incidence of treatment failures than daily regimens.…”

mentioning

confidence: 99%

Population pharmacokinetics of dapsone administered biweekly to human immunodeficiency virus-infected patients

Gatti

Merighi

Hossein

et al. 1996

Antimicrob Agents Chemother

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The population pharmacokinetics of dapsone were examined in human immunodeficiency virus-infected patients receiving dapsone at a dosage of 100 mg twice weekly for the prevention of Pneumocystis carinii pneumonia. Nonlinear mixed-effect modeling was used to determine the best pharmacostatistical model for the data. A one-compartment open model with first-order absorption and elimination was used as the structural pharmacokinetic model. Several covariates were tested for their influence on pharmacokinetic parameters. Rifampin was found to increase the values of clearance/bioavailability (CL/F) and volume of distribution/ bioavailability (V/F) by approximately 70%. CL/F and V/F were 1.83 liters/h and 69.6 liters, respectively, for patients not taking rifampin. The effect of rifampin on the pharmacokinetic parameters of dapsone was appreciably less than expected on the basis of studies with healthy volunteers. Increased bilirubin levels were associated with a significant decrease in the absorption rate constant (K a ). However, this finding may be considered clinically irrelevant because the post hoc Bayesian estimates of K a for patients with high bilirubin levels (>1.2 mg/dl) were at the lower bound of the values for patients with normal bilirubin levels. The value of K a was 0.957 h ؊1 for a patient with a bilirubin level of 0.7 mg/dl. After inclusion of covariates in the model, the interpatient variability was 35% for CL/F, not significant for V/F, and 85% for K a . Simulation of plasma concentration-versus-time curves indicated that the administration of 100 mg of dapsone biweekly is associated with sustained dapsone levels in the plasma of the majority of the patients. Dosage adjustments for patients concomitantly treated with rifampin may be necessary.

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“…Failure of PCP prophylaxis both with co‐trimoxazole and pentamidine is uncommon. It was shown in most studies that aerosolized pentamidine is effective for prevention of PCP despite a certain degree of its inferiority compared with TMP/SMX in AIDS and post‐BMT setting (22–26). In a randomized prospective multicentric clinical trial, equal efficacy of aerosolized pentamidine and cotrimoxazole for PCP prophylaxis was shown in HIV‐infected patients (27).…”

Section: Discussionmentioning

confidence: 99%

Is Pneumocystis carinii pneumonia after stem cell transplantations a contagious disease?

Resnick¹,

Averbuch²,

Aker³

et al. 2005

Clinical Transplantation

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We report of twins who underwent hematopoietic stem cell transplantation (HSCT) for neonatal acute leukemia. Hospitalized in the same room from the time the first one demonstrated respiratory symptoms, they both developed Pneumocystis jiroveci (formerly carinii) pneumonia (PCP) 2 wk apart. This observation suggests that PCP may be a contagious disease in HSCT recipients. This may be especially true for infants and young children who are at risk of primary P. jiroveci infection, and should be avoided.

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A Comparison of the Effectiveness of Three Regimens in the Prevention of Pneumocystis carinii Pneumonia in Human Immunodeficiency Virus-Infected Patients

Cited by 49 publications

References 19 publications

Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data

Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data

Population pharmacokinetics of dapsone administered biweekly to human immunodeficiency virus-infected patients

Is Pneumocystis carinii pneumonia after stem cell transplantations a contagious disease?

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