Assuntos
Antirretrovirais/administração & dosagem , Aspergilose/tratamento farmacológico , Citocromo P-450 CYP2C19/genética , Soropositividade para HIV/tratamento farmacológico , Voriconazol/administração & dosagem , Antirretrovirais/uso terapêutico , Aspergilose/genética , Cálculos da Dosagem de Medicamento , Soropositividade para HIV/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Voriconazol/uso terapêuticoAssuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Emtricitabina/administração & dosagem , Infecções por HIV/tratamento farmacológico , Tenofovir/administração & dosagem , Adenina/administração & dosagem , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos , Resultado do Tratamento , Carga Viral/efeitos dos fármacosAssuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV/efeitos dos fármacos , Ritonavir/uso terapêutico , Idoso , Cobicistat/uso terapêutico , Dabigatrana/uso terapêutico , Darunavir/uso terapêutico , Humanos , MasculinoRESUMO
PURPOSE: The pharmacokinetic interaction of etravirine and raltegravir is reviewed, with discussion of implications for clinical practice. SUMMARY: Etravirine (a second-generation nonnucleoside reverse transcriptase inhibitor) and raltegravir (an integrase strand- transfer inhibitor) are two agents approved by the Federal Food and Drug Administration for use in human immunodeficiency virus (HIV) treatment-resistant patients. Minimal data exist on the concurrent use of raltegravir with etravirine. This combination would offer treatment-experienced HIV patients a novel pharmacotherapy plan including two new fully active agents. Etravirine induces uridine diphosphate- glucuronosyltransferase 1A1 and reduces the raltegravir minimum concentration (C(min)) by 34% when administered concurrently in healthy volunteers. In a case series of four HIV treatment-resistant patients initiated on an antiretroviral regimen including standard doses of etravirine and raltegravir, poor virological control was demonstrated. Two of these four patients had a raltegravir C(min) below the 95% minimum inhibitory concentration. In a larger study (n = 103), sustained virological control (viral loads of <50 copies/mL) resulted when HIV treatment-resistant patients received standard doses of darunavir, ritonavir, etravirine, raltegravir, and nucleoside analogs with or without enfuvirtide. Debate exists regarding the best raltegravir pharmacokinetic parameter to evaluate (C(min) or the area under the concentration curve/50% effective concentration). Recent data in HIV treatment-naive patients support a negative association between a low raltegravir C(min) (≤43 ng/mL) and virological suppression. CONCLUSION: The need to adjust the dosage of raltegravir in HIV-infected patients who are also receiving etravirine is unclear. In such patients who have an extensive history of HIV disease treatment, prescribing raltegravir 1200 mg/day, rather than the standard 800 mg/day, may be prudent to prevent the development of treatment-resistant virus and to achieve an optimal virological response.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Piridazinas/farmacologia , Pirrolidinonas/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/farmacologia , Área Sob a Curva , Relação Dose-Resposta a Droga , Interações Medicamentosas , Farmacorresistência Viral , Quimioterapia Combinada , Glucuronosiltransferase/efeitos dos fármacos , Glucuronosiltransferase/metabolismo , Infecções por HIV/virologia , Inibidores de Integrase de HIV/administração & dosagem , Inibidores de Integrase de HIV/farmacocinética , Humanos , Nitrilas , Piridazinas/administração & dosagem , Pirimidinas , Pirrolidinonas/farmacocinética , Raltegravir Potássico , Carga Viral/efeitos dos fármacosRESUMO
A case of psoriasis and psoriatic arthritis in a 38-year-old white male patient infected with human immunodeficiency virus (HIV) treated safely and effectively with mycophenolate mofetil (MMF) is reported. Treatments for psoriasis and psoriatic arthritis are manifold, including topical, oral, intramuscular, intravenous, and subcutaneous therapies. These indicated treatments for psoriasis and psoriatic arthritis result in suppression of the immune system.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Infecções por HIV/complicações , Ácido Micofenólico/análogos & derivados , Psoríase/complicações , Psoríase/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Artrite Psoriásica/patologia , Clobetasol/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Psoríase/patologia , Pele/patologiaRESUMO
Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) has resulted in significant morbidity and mortality reductions. Lifelong antiretroviral therapy must be incorporated into each patient's medical regimen. Patients with HIV may also have simultaneous chronic medical conditions, resulting in the possibility of complex drug-drug interactions. We report a possible drug-drug interaction between HAART and warfarin in two patients, as assessed by the Naranjo adverse drug reaction probability scale and the Drug Interaction probability scale. Both patients' pharmacotherapy regimens included a nonnucleoside reverse transcriptase inhibitor (NNRTI), nevirapine, or a protease inhibitor, nelfinavir or lopinavir-ritonavir, and two nucleoside analogs. In both patients, high warfarin doses were required to maintain therapeutic international normalized ratios (INRs). Warfarin has two enantiomers, R-and S-warfarin, which are substrates primarily of cytochrome P450 (CYP) 3A4 (R-warfarin), CYP1A2 (R-warfarin), and CYP2C9 (S-warfarin). Protease inhibitors and NNRTIs have variable effects on CYP: induction, inhibition, or mixed. The increased warfarin doses required in these two patients may have been caused by induction of CYP3A4 by nevirapine, CYP2C9 by nelfinavir, or CYP2C9 by lopinavir-ritonavir. Thus, practitioners should prudently monitor INRs in patients receiving warfarin with concomitant HAART that includes either a protease inhibitor or an NNRTI.
Assuntos
Anticoagulantes/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Varfarina/efeitos adversos , Adulto , Combinação de Medicamentos , Interações Medicamentosas , Humanos , Lopinavir , Pessoa de Meia-Idade , Nelfinavir/efeitos adversos , Nevirapina/efeitos adversos , Inibidores de Proteases/efeitos adversos , Pirimidinonas/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Ritonavir/efeitos adversosRESUMO
OBJECTIVE: To report a case of pancreatitis associated with the combined use of didanosine and tenofovir. CASE SUMMARY: A 51-year-old white man with HIV was initiated on antiretroviral therapy with didanosine 250 mg/day, tenofovir 300 mg/day, lamivudine 300 mg/day, stavudine 60 mg/day, and efavirenz 600 mg/day. Didanosine was prescribed at a reduced dosage due to the known interaction with tenofovir. Despite this dosage adjustment, the patient developed acute pancreatitis 10 weeks after antiretrovirals were initiated. Pancreatitis resolved spontaneously after antiretroviral discontinuation. DISCUSSION: Our report of didanosine-induced pancreatitis secondary to concurrent use with tenofovir is the third reported case that utilized a reduced didanosine dosage. Five previous pancreatitis reports have been described using full-strength didanosine with tenofovir. The exact mechanism of action for this interaction is unknown. Utilizing the Naranjo probability scale to assess causality, a possible adverse drug reaction was determined. CONCLUSIONS: Tenofovir and didanosine may be used cautiously in antiretroviral combination therapy. Reduced didanosine dosage (250 mg) should be used to reduce serum didanosine concentrations and subsequent toxicities. Practitioners should be aware that a significant drug interaction with resulting pancreatitis may occur even when a reduced dosage is prescribed.