"The U.S. Food and Drug Administration is alerting hospitals, health care professionals, and patients of a voluntary recall of all non-expired drug products produced and distributed for sterile use by Abrams Royal Compounding Pharmacy in Dallas, T"...
Elevations of liver transaminases may occur in patients receiving PRIFTIN [see ADVERSE REACTIONS]. Patients on PRIFTIN should be monitored for symptoms of liver injury.
Patients with abnormal liver tests and/or liver disease or patients initiating treatment for active pulmonary tuberculosis should only be given PRIFTIN in cases of necessity and under strict medical supervision. In such patients, obtain serum transaminase levels prior to therapy and every 2-4 weeks while on therapy. Discontinue PRIFTIN if evidence of liver injury occurs.
Hypersensitivity And Related Reactions
Hypersensitivity reactions may occur in patients receiving PRIFTIN. Signs and symptoms of these reactions may include hypotension, urticaria, angioedema, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, fever, chills, aches, rash, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations). There have been reports of anaphylaxis [see PATIENT INFORMATION].
Monitor patients receiving PRIFTIN therapy for signs and/or symptoms of hypersensitivity reactions. If these symptoms occur, administer supportive measures and discontinue PRIFTIN.
Relapse In The Treatment Of Active Pulmonary Tuberculosis
Do not use PRIFTIN as a once-weekly continuation phase regimen in HIV-infected patients with active pulmonary tuberculosis because of a higher rate of failure and/or relapse with rifampinresistant organisms [see Clinical Studies].
Higher relapse rates may occur in patients with cavitary pulmonary lesions and/or positive sputum cultures after the initial phase of active tuberculosis treatment and in patients with evidence of bilateral pulmonary disease. Monitor for signs and symptoms of TB relapse in these patients [see Clinical Studies].
Poor adherence to therapy is associated with high relapse rate. Emphasize the importance of compliance with therapy [see PATIENT INFORMATION]
Rifapentine is an inducer of CYP450 enzymes. Concomitant use of rifapentine with other drugs metabolized by these enzymes, such as protease inhibitors, certain reverse transcriptase inhibitors, and hormonal contraception may cause a significant decrease in plasma concentrations and loss of therapeutic effect [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].
Discoloration Of Body Fluids
PRIFTIN may produce a red-orange discoloration of body tissues and/or fluids (e.g., skin, teeth, tongue, urine, feces, saliva, sputum, tears, sweat, and cerebrospinal fluid). Contact lenses or dentures may become permanently stained.
Clostridium difficile-Associated Diarrhea
Clostridium difficile-associated diarrhea (CDAD) has been reported with the use of nearly all systemic antibacterial agents, including PRIFTIN, with severity ranging from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon and may permit overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, discontinue antibacterial use not directed against C. difficile if possible. Institute appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation as clinically indicated.
Porphyria has been reported in patients receiving rifampin, attributed to induction of delta amino levulinic acid synthetase. Because PRIFTIN may have similar enzyme induction properties, avoid the use of PRIFTIN in patients with porphyria.
Patient Counseling Information
Emphasize the importance of compliance with the full course of therapy, and the importance of not missing any doses of PRIFTIN or companion medications in the treatment of active pulmonary tuberculosis or the treatment of latent tuberculosis infection.
Inform patients that PRIFTIN may cause hypersensitivity reactions. Signs and symptoms of this reaction may include a flu-like illness, hypotension, urticaria, angioedema, bronchospasm, conjunctivitis, thrombocytopenia or neutropenia. Anaphylaxis may also occur [see WARNINGS AND PRECAUTIONS].
Inform patients of signs and symptoms of hypersensitivity reactions and advise them to stop the medication and contact their healthcare provider if they experience any of these symptoms.
Instruct patients to stop the medication and notify their physician promptly if they experience any of the following: fever, loss of appetite, malaise, nausea and vomiting, darkened urine, yellowish discoloration of the skin and eyes, and pain or swelling of the joints [see WARNINGS AND PRECAUTIONS].
Rifapentine may increase the metabolism and decrease the activity of other drugs that are metabolized by the P4503A4 and 2C8/9 pathways. Dosage adjustments of the co-administered drugs may be necessary. Advise patients to discuss with their physician any other medications they are taking before starting treatment with PRIFTIN. [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS]
Concomitant use of PRIFTIN with protease inhibitors or reverse transcriptase inhibitors may cause a significant decrease in plasma concentrations and loss of therapeutic effect of the protease inhibitor or reverse transcriptase inhibitor. [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS]
Rifapentine may reduce the effectiveness of hormonal contraceptives. Advise patients using oral, transdermal patch, or other systemic hormonal contraceptives to change to non-hormonal methods of birth control. [see DRUG INTERACTIONS]
Discoloration Of Body Fluids
Inform the patient that PRIFTIN produces a reddish coloration of the urine, sweat, sputum, tears, and breast milk. Contact lenses or dentures may be permanently stained. [see WARNINGS AND PRECAUTIONS].
Administration With Food
Advise patients to take PRIFTIN with food.
Advise nursing mothers that breastfeeding is not recommended with PRIFTIN use [see Use In Specific Populations].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Hepatocellular carcinomas were increased in male NMRI mice (Harlan Winklemann) which were treated orally with rifapentine for two years at or above doses of 5 mg/kg/day (0.04 times the recommended human dose based on body surface area conversions). In a two year rat study, there was an increase in nasal cavity adenomas in Wistar rats treated orally with rifapentine at 40 mg/kg/day (0.6 times human dose based on body surface area conversions).
Rifapentine was negative in the following genotoxicity tests: in vitro gene mutation assay in bacteria (Ames test); in vitro point mutation test in Aspergillus nidulans; in vitro gene conversion assay in Saccharomyces cerevisiae; host-mediated (mouse) gene conversion assay with Saccharomyces cerevisiae; in vitro Chinese hamster ovary cell/hypoxanthineguaninephosphoribosyl transferase (CHO/HGPRT) forward mutation assay; in vitro chromosomal aberration assay utilizing rat lymphocytes; and in vivo mouse bone marrow micronucleus assay.
The 25-desacetyl metabolite of rifapentine was positive in the in vitro mammalian chromosome aberration test in V79 Chinese Hamster cells, but was negative in the in vitro gene mutation assay in bacteria (Ames test), the in vitro Chinese hamster ovary cell/hypoxanthine-guaninephosphoribosyl transferase (CHO/HGPRT) forward mutation assay, and the in vivo mouse bone marrow micronucleus assay. Fertility and reproductive performance were not affected by oral administration of rifapentine to male and female rats at doses of up to 20 mg/kg/day (one-third of the human dose based on body surface area conversions).
Use In Specific Populations
Pregnancy Category C
There are no adequate and well controlled trials of PRIFTIN in pregnant women; however, there are limited pregnancy outcome data reported from women enrolled in clinical trials of various PRIFTIN treatment regimens for active tuberculosis and latent tuberculosis infection. The reported rate of spontaneous abortion following PRIFTIN exposure did not represent an increase over the background rate of spontaneous abortion reported in the general population. Further interpretation of these data is limited by the quality of clinical trial adverse event reporting. In animal reproduction and developmental toxicity studies, rifapentine produced fetal harm and was teratogenic at doses less than and similar to the recommended human dose. Because animal studies are not always predictive of human response, PRIFTIN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor or Delivery
When administered during the last few weeks of pregnancy, rifampin, another rifamycin product, may increase the risk for maternal postpartum hemorrhage and bleeding in the exposed neonate. Monitor prothrombin time of pregnant women and neonates, who are exposed to PRIFTIN during the last few weeks of pregnancy. Treatment with Vitamin K may be indicated.
Fourteen patients with active tuberculosis treated with multiple anti-tuberculosis drugs including PRIFTIN became pregnant during clinical studies. Six delivered normal infants; four had first trimester spontaneous abortions (of these, one patient abused ethanol and another patient was HIV-infected); one had an elective abortion; and outcome was unknown in three patients. These data are, however, limited by the quality of reporting and confounded by co-morbid medical conditions and multiple anti-tuberculosis drug exposures.
In the trial that compared the safety and effectiveness of PRIFTIN in combination with isoniazid to isoniazid alone for the treatment of latent tuberculosis infection, a total of 45 (2.5%) women in the PRIFTIN/isoniazid arm and 71 (4.1%) women in the isoniazid arm became pregnant. Among the 46 total pregnancies in the PRIFTIN/isoniazid arm, there were 31 live births, six elective abortions, seven spontaneous abortions, and two unknown outcomes. Of the 31 live infants, 21 were reported healthy while in the other ten cases no further details were available. No congenital anomalies were reported. The rate of spontaneous abortion in the PRIFTIN/isoniazid arm (15%), and the rate of spontaneous abortion in the isoniazid arm (19%), did not represent an increase over the background rate of 15 to 20 percent reported in the general population. Further interpretation of these results is limited by the quality of adverse event reporting.
Animal studies in rats and rabbits revealed embryofetal toxicity in both species. Pregnant rats given oral rifapentine during organogenesis at 40 mg/kg/day (0.6 times the human dose of 600 mg 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 orally to mated female rats late in gestation, at 20 mg/kg/day (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 oral rifapentine at 10 mg/kg to 40 mg/kg (0.3 times 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.
It is not known whether PRIFTIN is present in 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 [see Nonclinical Toxicology]. Since PRIFTIN 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.
The safety and effectiveness of PRIFTIN in the treatment of active pulmonary tuberculosis have not been established in pediatric patients under the age of 12.
The safety and effectiveness of PRIFTIN in combination with isoniazid once-weekly regimen has been evaluated in pediatric patients (2-17 years of age) for the treatment of latent tuberculosis infection. In clinical studies, the safety profile in children was similar to that observed in adult patients [see ADVERSE REACTIONS and Clinical Studies].
In a pharmacokinetic study conducted in 2 year to 11 year-old pediatric patients with latent tuberculosis infection, PRIFTIN was administered once-weekly based on weight (15mg/kg to 30 mg/Kg, up to a maximum of 900 mg). Exposures (AUC) in children 2 years-11 years with latent tuberculosis infection were higher (average 31%) than those observed in adults receiving PRIFTIN 900mg once-weekly [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
Clinical studies with PRIFTIN did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. In a pharmacokinetic study with PRIFTIN, no substantial differences in the pharmacokinetics of rifapentine and 25desacetyl metabolite were observed in the elderly compared to younger adults [see CLINICAL PHARMACOLOGY].
Last reviewed on RxList: 12/16/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Priftin Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.