Rifapentine indications and usage: Difference between revisions
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Rifapentine should not be used as monotherapy in either the initial or the continuation phases of antituberculous treatment.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = PRIFTIN (RIFAPENTINE) TABLET, FILM COATED [SANOFI-AVENTIS U.S. LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f768e337-a948-420a-9fbe-9be359c7a170 | publisher = | date = | accessdate = }}</ref> | Rifapentine should not be used as monotherapy in either the initial or the continuation phases of antituberculous treatment.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = PRIFTIN (RIFAPENTINE) TABLET, FILM COATED [SANOFI-AVENTIS U.S. LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f768e337-a948-420a-9fbe-9be359c7a170 | publisher = | date = | accessdate = }}</ref> | ||
==Use In Specific Populations== | |||
===Pregnancy=== | |||
====Pregnancy Category C==== | |||
There are no adequate and well controlled studies of rifapentine use during pregnancy. In animal reproduction and developmental toxicity studies, rifapentine produced fetal harm and was teratogenic. However, because animal studies are not always predictive of human response, rifapentine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. | |||
When administered during the last few weeks of pregnancy, rifampin, another rifamycin, may increase the risk for maternal postpartum hemorrhage and bleeding in the exposed infant. Therefore, pregnant women and their infants, who are exposed to rifapentine during the last few weeks of pregnancy, should have appropriate monitoring of clotting parameters. Treatment with Vitamin K may be indicated. | |||
Six patients randomized to rifapentine became pregnant during a study of initial treatment of tuberculosis. Two delivered normal infants; two had first trimester spontaneous abortions; one had an elective abortion; and one patient was lost to follow-up. The two patients who spontaneously aborted had co-morbid conditions: One patient abused ethanol and the other patient was HIV positive. | |||
Animal studies in rats and rabbits revealed embryofetal toxicity in both species. Pregnant rats given rifapentine during organogenesis at doses 0.6 times the human dose (based on body surface area), produced pups with cleft palates, right aortic arch, increased incidence of delayed ossification, and increased numbers of ribs. When rifapentine was administered to mated female rats late in gestation, at 0.3 times the human dose (based on body surface area), pup weights and gestational survival (live pups born/pups born) were reduced compared to controls. Increased resorptions and post implantation loss, decreased mean fetal weights, increased numbers of stillborn pups, and slightly increased pup mortality during lactation were also noted. When pregnant rabbits received rifapentine at doses 0.3 to 1.3 times the human dose (based on body surface area), major fetal malformations occurred including: [[ovarian agenesis]], [[pes varus]], [[arhinia]], [[microphthalmia]] and irregularities of the ossified facial tissues. At the higher dose, there were increases in post-implantation loss and the incidence of stillborn pups. | |||
===Nursing Mothers=== | |||
It is not known whether rifapentine is excreted into human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother and the benefits of breastfeeding. Since rifapentine may produce a red-orange discoloration of body fluids, there is a potential for discoloration of breast milk. | |||
A slight increase in rat pup mortality was observed during lactation when dams were dosed late in gestation through lactation. | |||
===Pediatric Use=== | |||
The safety and effectiveness of rifapentine in pediatric patients under the age of 12 have not been established. In a pharmacokinetic study conducted in 2 to 12 year-old pediatric patients, the exposure to rifapentine (i.e., AUC and Cmax) was lower compared with that observed in healthy adults [see Clinical Pharmacology ]. Another pharmacokinetic study was conducted in 12 to 15 year-old healthy volunteers and the pharmacokinetics of rifapentine were similar to those observed in healthy adults [see Clinical Pharmacology]. | |||
===Geriatric Use=== | |||
The Clinical studies of PRIFTIN did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see Clinical Pharmacology ]. | |||
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==References== | ==References== | ||
Revision as of 04:08, 6 January 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Indications And Usage
Rifapentine is indicated for the treatment of pulmonary tuberculosis caused by Mycobacterium tuberculosis. Rifapentine must always be used in combination with one or more antituberculosis drugs to which the isolate is susceptible depending on the phase of treatment [see Dosage and Administration and Clinical Studies .
Limitations of Use
Rifapentine should not be used as a once weekly Continuation Phase regimen in combination with isoniazid in HIV seropositive patients with pulmonary tuberculosis because of a higher rate of failure and/or relapse documented with the presence of rifampin-resistant organisms [see Warnings and Precautions and Clinical Studies ].
Rifapentine has not been studied as part of the Initial Phase treatment regimen in HIV seropositive patients with pulmonary tuberculosis.
Rifapentine should not be used as monotherapy in either the initial or the continuation phases of antituberculous treatment.[1]
Use In Specific Populations
Pregnancy
Pregnancy Category C
There are no adequate and well controlled studies of rifapentine use during pregnancy. In animal reproduction and developmental toxicity studies, rifapentine produced fetal harm and was teratogenic. However, because animal studies are not always predictive of human response, rifapentine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
When administered during the last few weeks of pregnancy, rifampin, another rifamycin, may increase the risk for maternal postpartum hemorrhage and bleeding in the exposed infant. Therefore, pregnant women and their infants, who are exposed to rifapentine during the last few weeks of pregnancy, should have appropriate monitoring of clotting parameters. Treatment with Vitamin K may be indicated.
Six patients randomized to rifapentine became pregnant during a study of initial treatment of tuberculosis. Two delivered normal infants; two had first trimester spontaneous abortions; one had an elective abortion; and one patient was lost to follow-up. The two patients who spontaneously aborted had co-morbid conditions: One patient abused ethanol and the other patient was HIV positive.
Animal studies in rats and rabbits revealed embryofetal toxicity in both species. Pregnant rats given rifapentine during organogenesis at doses 0.6 times the human dose (based on body surface area), produced pups with cleft palates, right aortic arch, increased incidence of delayed ossification, and increased numbers of ribs. When rifapentine was administered to mated female rats late in gestation, at 0.3 times the human dose (based on body surface area), pup weights and gestational survival (live pups born/pups born) were reduced compared to controls. Increased resorptions and post implantation loss, decreased mean fetal weights, increased numbers of stillborn pups, and slightly increased pup mortality during lactation were also noted. When pregnant rabbits received rifapentine at doses 0.3 to 1.3 times the human dose (based on body surface area), major fetal malformations occurred including: ovarian agenesis, pes varus, arhinia, microphthalmia and irregularities of the ossified facial tissues. At the higher dose, there were increases in post-implantation loss and the incidence of stillborn pups.
Nursing Mothers
It is not known whether rifapentine is excreted into human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother and the benefits of breastfeeding. Since rifapentine may produce a red-orange discoloration of body fluids, there is a potential for discoloration of breast milk.
A slight increase in rat pup mortality was observed during lactation when dams were dosed late in gestation through lactation.
Pediatric Use
The safety and effectiveness of rifapentine in pediatric patients under the age of 12 have not been established. In a pharmacokinetic study conducted in 2 to 12 year-old pediatric patients, the exposure to rifapentine (i.e., AUC and Cmax) was lower compared with that observed in healthy adults [see Clinical Pharmacology ]. Another pharmacokinetic study was conducted in 12 to 15 year-old healthy volunteers and the pharmacokinetics of rifapentine were similar to those observed in healthy adults [see Clinical Pharmacology].
Geriatric Use
The Clinical studies of PRIFTIN did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see Clinical Pharmacology ].
References
Adapted from the FDA Package Insert.