ライフサイエンスコーパス: rifapentine

1 hieve highly active once-weekly therapy with rifapentine.

2 der than 64 years treated with isoniazid and rifapentine.

3 wed increased susceptibility to rifampin and rifapentine.

4 ng a 12-dose regimen of weekly isoniazid and rifapentine.

5 evaluation of the safety and tolerability of rifapentine 1,200 mg is warranted.

6 Only one discontinuation, in the rifapentine 1,200-mg arm, was due to an adverse event po

7 ve pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, adm

8 .4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups.

9 ositive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg dai

10 were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, res

11 continuation phase regimen of isoniazid plus rifapentine (10 mg/kg) is inferior to standard twice-wee

12 renz (EFV2) received TB treatment containing rifapentine (1200 mg), isoniazid, pyrazinamide, and eith

13 detected between once-weekly isoniazid plus rifapentine (15 mg/kg) and the Denver regimen.

14 ng activity of once-weekly moxifloxacin plus rifapentine (15 mg/kg) was significantly greater than th

15 I with 3 months of once-weekly isoniazid and rifapentine (3HP) administered under directly observed t

16 s of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Imme

17 ventive regimen such as weekly isoniazid and rifapentine (3HP) for 3 months is a priority for tubercu

18 12-week regimen of once-weekly isoniazid and rifapentine (3HP) is currently recommended by the CDC as

19 A 3-month regimen of weekly isoniazid and rifapentine (3HP) is safe and effective for tuberculosis

20 tested three months of weekly isoniazid and rifapentine (3HP) plus daily cART.

21 TB) prevention such as once weekly isoniazid-rifapentine (3HP) taken for 3 months is a key priority f

22 continuation was with 3 months isoniazid and rifapentine (3HP), and the lowest was with 4 months rifa

23 zid (6H) or 3 months of weekly isoniazid and rifapentine (3HP), delivered by the Indus Health Network

24 kly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of ison

25 pin (3RH) and three months of isoniazid plus rifapentine (3RPTH).

26 Once-weekly rifapentine 600 mg plus isoniazid (INH) during the conti

27 (6%), 2 of 51 (4%), and 3 of 47 (6%) in the rifapentine 600-, 900-, and 1,200-mg treatment arms, res

28 Rifapentine 900-mg, once-weekly dosing appears to be saf

29 f directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combinatio

30 ventive therapy with 12 doses of once-weekly rifapentine (900 mg) plus isoniazid (900 mg) could great

31 not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for

32 favirenz for 8 weeks, then began once-weekly rifapentine (900 mg)-isoniazid (900 mg) for 12 weeks.

33 months of once-weekly isoniazid (900 mg) and rifapentine (900 mg; 3HP) is a recommended option for pe

34 Rifapentine administered 5 days per week has potent acti

35 onths followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a

36 Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MR

37 In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians

38 evaluation of drug-drug interactions between rifapentine and efavirenz.

39 ne; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin.

40 ic medical support, widespread use of weekly rifapentine and isoniazid (3HP) for latent tuberculosis

41 Weekly rifapentine and isoniazid (3HP) is gaining popularity fo

42 for LTBI with 3 months of self-administered rifapentine and isoniazid (3HP) under various TTT scenar

43 LTBI with three months of self-administered rifapentine and isoniazid (3HP) under various TTT scenar

44 ith HIV, but all women achieved exposures of rifapentine and isoniazid associated with successful tub

45 Three months of a once-weekly combination of rifapentine and isoniazid for treatment of latent tuberc

46 died the interaction of efavirenz with daily rifapentine and isoniazid in human immunodeficiency viru

47 Despite incorporation of 1 month of rifapentine and isoniazid into global guidelines, curren

48 Treatment with the combination of rifapentine and isoniazid was as effective as isoniazid-

49 mean ratio (GMR) of values before and during rifapentine and isoniazid was calculated.

50 Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokin

51 A 4-month regimen containing rifapentine and moxifloxacin has noninferior efficacy co

52 included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the con

53 e evaluated new treatment regimens including rifapentine and moxifloxacin, and assessed the potential

54 and protein-bound) plasma concentrations of rifapentine and of desacetyl rifapentine detected for mo

55 n the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, i

56 ression analyses, AUC(0-infinity) values for rifapentine and the active 25-desacetyl metabolite were

57 one or with oral bedaquiline with or without rifapentine), and four comparator regimens consisted of

58 t the binding sites for rifampin, rifabutin, rifapentine, and sorangicin A are shared, whereas the bi

59 ing two rifamycin derivatives, rifabutin and rifapentine, and streptolydigin and sorangicin A, which

60 th 2 weeks of oral bedaquiline and high-dose rifapentine; and two injections with 4 weeks of oral bed

61 We detected anti-rifapentine, anti-isoniazid, and anti-rifapentine metabo

62 prevention regimens containing rifampicin or rifapentine are as effective as longer, isoniazid-based

63 er among rifapentine recipients who had high rifapentine areas under the concentration-time curve.

64 The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied durin

65 ility, safety, and antimicrobial activity of rifapentine at daily doses of up to 20 mg/kg of body wei

66 ospective, randomized, double-blind trial of rifapentine at three doses (600, 900, and 1,200 mg) plus

67 nfinity)) increased significantly with dose (rifapentine AUC(0- infinity): 296, 410, and 477 microg.h

68 of 35 cases; 3%) and not linked with higher rifapentine AUC(0-infinity) or peak concentration.

69 sterilizing activity of improved once-weekly rifapentine-based continuation phase regimens in a murin

70 The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was no

71 Fewer AEs were reported in rifapentine-based regimens (15%) than the control regime

72 Combinations of short-course rifapentine-based regimens and integrase strand-transfer

73 experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer

74 e optimal dosing strategies for short-course rifapentine-based regimens for latent tuberculosis infec

75 Rifapentine-based regimens have potent antimycobacterial

76 s from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regim

77 9, an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regim

78 ticipants received once-weekly isoniazid and rifapentine by direct observation, self-administration w

79 Once-weekly isoniazid-rifapentine by self-administered therapy (3HP-SAT) has n

80 Once-weekly isoniazid-rifapentine by self-administered therapy (3HP-SAT) has n

81 tion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observa

82 Rifapentine clearance is higher among women with HIV, bu

83 Three-month, once-weekly regimens of rifapentine combined with either isoniazid or moxifloxac

84 ars, a treat-all approach with isoniazid and rifapentine compared with a treat-TST-only approach led

85 e efficacy of the once-weekly isoniazid plus rifapentine continuation phase regimen can be increased

86 atients treated with a once-weekly isoniazid/rifapentine continuation-phase regimen.

87 for isoniazid and an increase in the dose of rifapentine could augment the activity of once-weekly re

88 ncentrations of rifapentine and of desacetyl rifapentine detected for more than 36 hours after cleara

89 orts further trials to determine the optimal rifapentine dose for treatment of tuberculosis.

90 The safety and tolerability of higher rifapentine doses need to be determined.

91 h/ml of rifapentine drug exposure (as measured by AUC) was 0.11

92 nonlinear mixed effects model in relation to rifapentine exposure (area under the concentration-time

93 Increasing rifapentine exposure is associated with a higher rate of

94 ng the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tubercul

95 Moreover, rifapentine exposure, but not assigned dose, was signifi

96 Notably, high rifapentine exposures are not associated with any predef

97 d to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to

98 High rifapentine exposures were associated with high levels o

99 Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by req

100 Once-weekly isoniazid and rifapentine for 12 weeks (3HP) or daily isoniazid for 9

101 A once-weekly oral dose of isoniazid and rifapentine for 3 months (3HP) is recommended by the CDC

102 ticipants who received weekly isoniazid plus rifapentine for 3 months (3HP) or daily isoniazid for 9

103 kly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months.

104 d with the positive control (daily isoniazid-rifapentine for 4 wk), six regimens had equivalent bacte

105 safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment.

106 ed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol

107 ized or who died after >=1 dose of isoniazid-rifapentine for treatment of latent Mycobacterium tuberc

108 Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted.

109 rifampin group and 133 of 196 (67.9%) in the rifapentine group (difference, 2.8%; 95% CI: -6.9, 12.4)

110 p and 171 of 198 participants (86.4%) in the rifapentine group (difference, 3.0%; 95% confidence inte

111 f five relapses in the once-weekly isoniazid/rifapentine group had monoresistance to rifamycin, compa

112 up and 40 of 275 participants (14.5%) in the rifapentine group prematurely discontinued treatment (P=

113 of 30 patients in the once-weekly isoniazid/rifapentine group relapsed, compared with three of 31 pa

114 fapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with hum

115 fapentine-moxifloxacin group, and 752 in the rifapentine group).

116 pentine-moxifloxacin group, and 14.3% in the rifapentine group.

117 Rationale: Rifapentine has been investigated at various doses, freq

118 Rifapentine has potent activity in mouse models of tuber

119 g participants with flu-like reactions; anti-rifapentine IgG antibodies were not present in any parti

120 In participants receiving 3HP, anti-rifapentine IgG was identified in 2 of 22 (9%) participa

121 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with ri

122 hort-course directly observed isoniazid plus rifapentine (INH/RPT) combination could have potential a

123 Rifapentine is a cyclopentyl-substituted rifamycin whose

124 One month of daily rifapentine + isoniazid (1HP) is an effective, ultrashor

125 niazid), at week 11 (after the third dose of rifapentine)-isoniazid and at week 16 after the eighth d

126 assays (ELISA) to detect antibodies against rifapentine, isoniazid, rifampin, and rifapentine metabo

127 Our results suggest 12 doses of once-weekly rifapentine-isoniazid can be given for tuberculosis prop

128 -0.56) though this ratio varied by day after rifapentine-isoniazid dose.

129 The methods were applied to the A5279/Brief Rifapentine-Isoniazid Efficacy for TB Prevention study,

130 Treatment completion was higher with rifapentine-isoniazid for 3 months compared with isoniaz

131 nts were randomly assigned to receive weekly rifapentine-isoniazid for 3 months, given either annuall

132 r death were 3.1 per 100 person-years in the rifapentine-isoniazid group, 2.9 per 100 person-years in

133 ompletion in the first year for the combined rifapentine-isoniazid groups (n = 3610) was 90.4% versus

134 Rifapentine-isoniazid increased dolutegravir clearance b

135 If rifapentine-isoniazid is effective in curing subclinical

136 s incidence among participants receiving the rifapentine-isoniazid regimen twice (n = 1808) or once (

137 Evidence existed for efficacy of weekly rifapentine-isoniazid regimens compared with no treatmen

138 of trough concentrations with versus without rifapentine-isoniazid was 0.53 (90% CI 0.49-0.56) though

139 r pharmacokinetic sampling at week 8 (before rifapentine-isoniazid), at week 11 (after the third dose

140 kinetics, assessed in participants who began rifapentine-isoniazid.

141 Participants received daily rifapentine/isoniazid (600 mg/300 mg) for 28 days as par

142 niazid (INH), 4-month rifampin (RIF), weekly rifapentine/isoniazid (RPT/INH) for 12 weeks, or no trea

143 d 9.8 L/hour (IQR, 7.04-15.59 L/hour) during rifapentine/isoniazid treatment (GMR, 1.04 [90% confiden

144 or 3 months of directly observed once-weekly rifapentine (maximum dose, 900 mg) plus isoniazid (maxim

145 eomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clini

146 However, rifapentine may decrease antiretroviral drug concentrati

147 h failure/relapse with once-weekly isoniazid/rifapentine (median isoniazid area under the concentrati

148 d anti-rifapentine, anti-isoniazid, and anti-rifapentine metabolite antibodies, but the proportions o

149 gainst rifapentine, isoniazid, rifampin, and rifapentine metabolite.

150 TB treatment containing high-dose daily rifapentine modestly decreased (rather than increased) e

151 losis, and a four-drug regimen of isoniazid, rifapentine, moxifloxacin, and pyrazinamide has become p

152 Together, these findings suggest that rifapentine, moxifloxacin, and, perhaps, therapeutic DNA

153 ticipants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapen

154 lation; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapenti

155 lation; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapenti

156 ated to the control and 9.2% (n = 70) to the rifapentine-moxifloxacin regimen dosed within the therap

157 dy 31/ACTG A5349 demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pu

158 The rifapentine-moxifloxacin regimen was noninferior to cont

159 uL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was noninferior to the

160 Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposu

161 L for the control and 226-349 mg.h/L for the rifapentine-moxifloxacin regimen.

162 fect of regimens containing daily, high-dose rifapentine on efavirenz pharmacokinetics and viral supp

163 andomly assigned 900 mg isoniazid and 600 mg rifapentine once weekly, or 900 mg isoniazid and 600 mg

164 Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous is

165 ctions can occur after exposure to rifampin, rifapentine, or isoniazid.

166 ated with outcome with once-weekly isoniazid/rifapentine (p = 0.03) but not twice-weekly isoniazid/ri

167 s for latent tuberculosis infection.Methods: Rifapentine pharmacokinetic studies were identified thou

168 Autoinduction of clearance was driven by rifapentine plasma concentrations.

169 acy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months

170 ine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART

171 tober 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rif

172 Three months of weekly rifapentine plus isoniazid (3HP) therapy for latent tube

173 Four weeks of daily rifapentine plus isoniazid can be coadministered with ef

174 (SDR) is a major safety concern with weekly rifapentine plus isoniazid for 12 doses (3HP) for latent

175 Weekly rifapentine plus isoniazid for 3 months (3HP) is as effe

176 The use of rifapentine plus isoniazid for 3 months was as effective

177 A 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months o

178 n = 6886) found that 3 months of once-weekly rifapentine plus isoniazid was noninferior to 9 months o

179 Rifapentine population pharmacokinetics were described s

180 roach is lacking.Objectives: To characterize rifapentine population pharmacokinetics, including autoi

181 the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas un

182 Using a new 2020 price for rifapentine reduced the cost per completed course of 3HP

183 onfidence interval [CI] -20.8% to 6.0%); the rifapentine regimen was not noninferior to control (+7.5

184 The rifapentine regimen was safe but not significantly more

185 not be treated with a once-weekly isoniazid/rifapentine regimen.

186 Twelve-week rifapentine (RPT)/isoniazid (INH) is effective for LTBI

187 patients.Conclusions: Weight-based dosing of rifapentine should be removed from clinical guidelines,

188 revention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for re

189 hange of CT was higher in subjects receiving rifapentine than in subjects receiving standard-dose rif

190 To understand why once-weekly isoniazid/rifapentine therapy for tuberculosis was less effective

191 for isoniazid and by increasing the dose of rifapentine to a clinically acceptable level of 15 mg/kg

192 self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in th

193 isoniazid (INH) alone or in combination with rifapentine to treat latent tuberculosis infections.

194 nion courses of bedaquiline, with or without rifapentine, using the validated mouse model of tubercul

195 red the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulm

196 d for 3-mo regimens containing rifampicin or rifapentine was 19-100%.

197 Among women without HIV, clearance of rifapentine was 28% lower during pregnancy than postpart

198 Rifapentine was more potent than rifampin prior to devel

199 Daily rifapentine was well-tolerated and safe.

200 gnificantly higher when using isoniazid plus rifapentine weekly for 3 months (3HP) and rifampicin dai

201 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin.

202 Isoniazid and rifapentine were provided at standard doses (900 mg/week

203 culosis antibiotics (rifampin, rifabutin and rifapentine) were compared in primary human hepatocytes.

204 , and UGT1A4/1A5 and predicted lower DDIs of rifapentine with 58 clinical drugs used to treat co-morb

205 Rifapentine with moxifloxacin was noninferior to the con

206 pared a once-weekly regimen of isoniazid and rifapentine with twice weekly isoniazid and rifampin in

207 Rifabutin or rifapentine with vancomycin were as active as rifampin w

208 Rifapentine without moxifloxacin was not shown to be non

209 and treatment with 3 months of isoniazid and rifapentine would avert 31 (95% uncertainty interval 14-