RESUMO
In light of recent reports of osteonecrosis of the jaw (ONJ) in cancer patients whose treatment regimens include an intravenous bisphosphonate, Novartis convened an international advisory board of experts in the fields of oral surgery and pathology, medical oncology, metabolic bone disease, and orthopedics to review existing data and provide updated recommendations on the clinical diagnosis, prevention, and management of ONJ in the oncology setting. Recommendations were developed to help guide healthcare professionals in early diagnosis and patient management. It is recommended that patients be encouraged to receive a dental examination prior to initiating bisphosphonate therapy and, if possible, complete any necessary dental procedures (e.g., tooth extraction) prior to initiating bisphosphonate therapy. Patients should receive regular dental visits during bisphosphonate therapy. Patients should be encouraged to practice good oral hygiene and minimize possible jaw trauma. If possible, patients should avoid dental surgery during treatment with bisphosphonates. If exposed bone is observed or reported in the oral cavity at any time (suspected ONJ), refer the patient to a dental professional immediately.
Assuntos
Doenças Maxilomandibulares/diagnóstico , Doenças Maxilomandibulares/prevenção & controle , Doenças Maxilomandibulares/terapia , Osteonecrose/diagnóstico , Osteonecrose/prevenção & controle , Osteonecrose/terapia , Difosfonatos/efeitos adversos , Guias como Assunto , Humanos , Osteoporose/tratamento farmacológicoRESUMO
Previously, we reported the efficacy of aliskiren/amlodipine in US minority adults with stage 2 hypertension, with additional blood pressure (BP) lowering from the addition of hydrochlorothiazide (HCTZ). A subgroup analysis in patients with hypertension and comorbidities of diabetes, cardiometabolic syndrome, or obesity, and in black participants is reported. This 8-week, multicenter, double-blind study included 412 self-identified minority patients with mean sitting systolic BP (msSBP) ≥160 mm Hg and <200 mm Hg). Patients were randomized to receive either combination aliskiren/amlodipine 150/5 mg or amlodipine 5 mg. Doses were forced-titrated to a maximum of aliskiren/amlodipine/HCTZ 300/10/25 mg or aliskiren/amlodipine 300/10 mg, respectively. There were 256 black (62%), 118 diabetic (29%), 284 cardiometabolic syndrome (69%), and 249 obese (60%) randomized patients. Baseline msSBP was ~167 mm Hg across all subgroups. Least-square mean reductions in msSBP, the primary efficacy outcome, from baseline to week 8 across all subgroups, ranged from 35 to 37 mm Hg with aliskiren/amlodipine/HCTZ and 28 to 30 mm Hg with aliskiren/amlodipine (P < .01 for all between-treatment comparisons). Both regimens were well tolerated. Among high-risk patients, such as diabetics or those with cardiometabolic syndrome, combination aliskiren/amlodipine is effective in lowering BP; the addition of HCTZ provided incremental BP-lowering efficacy while maintaining tolerability. However, because our subgroups were not mutually exclusive, the generalization of our findings to the population seen in clinical practice is limited.
Assuntos
Amidas/administração & dosagem , Anlodipino/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Fumaratos/administração & dosagem , Hidroclorotiazida/administração & dosagem , Hipertensão/tratamento farmacológico , Grupos Minoritários , Adulto , Bloqueadores dos Canais de Cálcio/administração & dosagem , Diuréticos/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hipertensão/etnologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Renina/antagonistas & inibidores , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Patients with stage 2 systolic hypertension require sizable blood pressure (BP) reductions to achieve recommended targets. This randomized double-blind study compared a single-pill combination of the direct renin inhibitor aliskiren and hydrochlorothiazide (aliskiren/HCTZ) with HCTZ monotherapy in older patients (older than 55 years) with systolic BP ≥160 mm Hg and <200 mm Hg. After a 1- to 4-week washout, 451 patients were randomized to once-daily aliskiren/HCTZ 150/12.5 mg or HCTZ 12.5 mg for 1 week, and then double the doses for 7 weeks. Overall baseline BP was 168.8/91.4 mm Hg. At week 4 (primary) end point, aliskiren/HCTZ provided significantly greater BP reductions from baseline than HCTZ monotherapy (29.6/9.3 mm Hg vs 22.3/6.8 mm Hg) and resulted in a greater proportion of patients achieving BP goal of <140/90 mm Hg (51.1% vs 33.3%). Aliskiren/HCTZ therapy provides substantial BP reductions and may thus be a useful treatment option for older patients with stage 2 hypertension.
Assuntos
Amidas/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Diuréticos/uso terapêutico , Fumaratos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Fatores Etários , Idoso , Análise de Variância , Pressão Sanguínea , Índice de Massa Corporal , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Indicadores Básicos de Saúde , Humanos , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Sístole , Resultado do Tratamento , Estados UnidosRESUMO
The renin-angiotensin system (RAS) is a common link between hypertension and comorbidities of obesity and metabolic syndrome (MetS). We evaluated the antihypertensive efficacy and safety of the combination direct renin inhibitor, aliskiren, with amlodipine versus amlodipine alone in self-identified African Americans with stage 2 hypertension in a subgroup of patients with obesity or MetS participating in the Aliskiren Amlodipine Combination in African AmEricans with Stage 2 HypertenSion (AACESS) trial. Subjects, newly diagnosed and treatment naive or taking three or fewer antihypertensive drugs with a mean sitting systolic blood pressure (msSBP) of 160-199 mm Hg were randomized to receive aliskiren/amlodipine 150/5 mg or amlodipine 5 mg for 1 week; force-titrated to aliskiren/amlodipine 300/10 mg or amlodipine 10 mg, for an additional 7 weeks. Overall, 292 obese (body mass index ≥30 kg/m(2)) and 197 MetS subjects had baseline msSBP ranging from 167.0 to 167.5 mm Hg. Least-square mean reductions from baseline to 8 weeks in msSBP, the primary efficacy variable, were significantly higher with aliskiren/amlodipine than with amlodipine in both obese (-33.7 mm Hg vs. -27.9 mm Hg; P < .001) and MetS subjects (-36.4 mm Hg vs. -28.5 mm Hg; P < .001). Both treatments were well tolerated. Aliskiren/amlodipine 300/10 mg is more effective than amlodipine 10 mg in African Americans with stage 2 hypertension and obesity or MetS.
Assuntos
Amidas/administração & dosagem , Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Fumaratos/administração & dosagem , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Comorbidade , Método Duplo-Cego , Combinação de Medicamentos , Humanos , Análise dos Mínimos Quadrados , Estudos ProspectivosRESUMO
Efficacy of antihypertensive agents on central blood pressure (BP) in African Americans is not well studied. The authors report on an 8-week double-blind, randomized study of African American patients with stage 2 hypertension that compared brachial and central BP responses (substudy of 53 patients) to combination aliskiren/hydrochlorthiazide (HCTZ) and amlodipine monotherapy. Following a 1- to 4-week washout, initial therapy was aliskiren/HCTZ 150/12.5 mg (n=166) or amlodipine 5 mg (n=166) for 1 week, forced-titrated to aliskiren/HCTZ 300/25 mg or amlodipine 10 mg for 7 weeks. Mean seated systolic BP reductions from baseline was similar with both treatments (-28.6 mm Hg with aliskiren/HCTZ vs -28.2 mm Hg with amlodipine). In the substudy, significantly greater reductions in central systolic BP was observed with aliskiren/HCTZ vs amlodipine (-30.1 mm Hg vs -21.2; P=.031), although 24-hour mean ambulatory BP reductions between the two groups were similar. Central pressure is considered an important risk factor in African Americans, and these findings may suggest a new treatment option for these patients.
Assuntos
Amidas/uso terapêutico , Anlodipino/uso terapêutico , Negro ou Afro-Americano , Pressão Sanguínea/fisiologia , Fumaratos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/etnologia , Adulto , Amidas/efeitos adversos , Amidas/farmacologia , Anlodipino/efeitos adversos , Anlodipino/farmacologia , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Artéria Braquial/fisiologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fumaratos/efeitos adversos , Fumaratos/farmacologia , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Hidroclorotiazida/efeitos adversos , Hidroclorotiazida/farmacologia , Hipertensão/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Minority patients with hypertension generally require combination therapy to reach blood pressure (BP) goals. We examined the BP-lowering efficacy and safety of combination aliskiren/amlodipine therapy in self-identified minority patients in the United States with stage 2 hypertension and the impact of adding hydrochlorothiazide (HCTZ) to this combination. In this 8-week double-blind study, 412 patients were randomized to receive aliskiren/amlodipine (150/5 mg) or amlodipine (5 mg) with forced titration up to aliskiren/amlodipine/HCTZ (300/10/25 mg) or aliskiren/amlodipine (300/10 mg), respectively. Overall, mean age was 55.2 years, mean body mass index was 32 kg/m(2), 62.3% were black, 28.2% were Hispanic/Latino, and 69.1% had metabolic syndrome. Mean sitting systolic blood pressure (MSSBP), the primary efficacy outcome, was reduced from 167.1 mm Hg at baseline to 130.7 mm Hg at week 8 with aliskiren/amlodipine/HCTZ and from 167.4 mm Hg to 137.9 mm Hg with aliskiren/amlodipine (P < .0001 between groups). At week 8, BP goal (<140/90 mm Hg) was achieved in 72.6% and 53.2% of patients in the two treatment groups, respectively (P < .0001). Adverse events were experienced by 34.2% and 40.2%, respectively. Combination aliskiren/amlodipine therapy was effective in treating these high-risk patients but inclusion of HCTZ provided greater antihypertensive efficacy. Both treatments were similarly well tolerated.
Assuntos
Amidas/administração & dosagem , Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Fumaratos/administração & dosagem , Hidroclorotiazida/administração & dosagem , Hipertensão/tratamento farmacológico , Hipertensão/etnologia , Amidas/efeitos adversos , Anlodipino/efeitos adversos , Anti-Hipertensivos/efeitos adversos , População Negra , Método Duplo-Cego , Combinação de Medicamentos , Monitoramento de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Fumaratos/efeitos adversos , Hispânico ou Latino , Humanos , Hidroclorotiazida/efeitos adversos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
DX-619 is a novel des-fluoro(6)-quinolone with activity against a broad range of bacterial strains, including methicillin-resistant Staphylococcus aureus. The effects of DX-619 on the glomerular filtration rate (GFR) were evaluated because drug-related increases in serum creatinine levels were observed in studies with healthy volunteers. Forty-one healthy subjects were randomized to receive intravenous DX-619 at 800 mg or placebo once daily for 4 days, and the GFR was directly measured by determination of the clearance of a bolus iohexol injection in 33 subjects who completed the study per protocol. DX-619 was noninferior to placebo for the GFR on the basis of a criterion for a clinically significant difference of -12 ml/min/1.73 m(2). The mean GFRs on day 4 were 101.1 +/- 14.2 ml/min/1.73 m(2) and 100.2 +/- 15.6 ml/min/1.73 m(2) for the volunteers receiving placebo and DX-619, respectively. On day 4 the mean serum creatinine concentration for volunteers receiving DX-619 increased by 30 to 40%, with a corresponding decrease in mean creatinine clearance. Both parameters normalized within 7 days after the cessation of DX-619 treatment. Nonclinical studies suggest that DX-619 increases the serum creatinine concentration by inhibiting excretory tubular transporters. In conclusion, DX-619 administered intravenously at 800 mg once a day for 4 days did not affect the GFR in healthy volunteers. Glomerular toxicity is not expected to present a risk to patients receiving DX-619 in clinical trials, but monitoring of the renal function, with an emphasis on the serum creatinine concentration, is still warranted.