Poor compliance with the dosage regimen, particularly the daily administered non-rifamycin drugs in the Intensive Phase, was associated with late sputum conversion and a high relapse rate in the rifapentine arm of Clinical Study 008. Therefore, compliance with the full course of therapy must be emphasized. and the importance of not missing any doses must be stressed.

(See

PRECAUTIONS

Since antituberculous muludrug treatment, including the rifamycin class, are associated with serious hepatic events, patients with abnormal liver tests and/or liver disease should only be given rifapentine in cases of necessity and then with caution and under strict medical supervision. In these patients careful monitoring of liver tests (especially serum transaminases) should be carried out prior to therapy and then every 2 to 4 weeks during therapy. If signs of liver disease occur or worsen alapentine should be discontinued.

Hyperbilirubinemia resulting from competition for excretory pathways between rifapentine and bilirubin cannot be excluded since competition between the related drug rifampin and bilirubin can occur. An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting treatment; rather, the decision should be made after repeating the tests, noting trends in the levels and considering them in conjunction with the patients clinical condition. Pscudomembranous colitis has been reported to occur with various antibiotics, including other rifamycins. Diarrhea, particularly if severe and/or persistent, occurring during treatment or in the initial weeks following treatment may be symptomatic of clostridium difficile-associated disease, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, rifapentine should be stopped immediately and the patient should be treated with supportive and specific treatment without delay (e.g., oral vancomycin). Products inhibiting peristalsis are contraindicated in this clinical situation.

Experience in HIV-infected patients is limited. In an ongoing CDC TB trial, five out of 30 HIV - infected patients randomized to once weekly rifapentine (plus INH) in the Continuation Phase who completed treatment, relapsed. Four of these patients developed rifampin mono-resistant (RMR) TB. Each RMR patient had late-stage HIV infection, low CD4 counts and extrapulmonary disease, and documented co-administration of antifungal azoles. These findings are consistent with the literature in which an emergence of RMR TB in HIV infected TB patients has been reported in recent years. Further study in this sub-population is warranted. As with other antituberculous treatments, when rifapentine is used in HIV-infected patients, a more aggressive regimen should be employed (e.g., more frequent dosing). Based on results to date of the CDC trial (See above), once weekly dosing during the continuation Phase of treatment is not recommended at this time.

Because rifapentine has been shown to increase indinavir metabolism (See DRUG INTERACTIONS), it should be used with extreme caution, if at all, in patients who are also taking protease inhibitors.

General

Rifapentine may produce a predominately 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 may become permanently stained.

Information for Patients.

The patient should be told that PRIFTIN may produce a reddish coloration of the urine, sweat, sputum, and tears, and the patient should be forewarned that contact lenses may be permanently stained. The patient should be advised that the reliability of oral or other systemic hormonal contraceptives may be affected; consideration should be given to using alternative contraceptive measures. For those patients with a propensity to nausea, vomiting, or gastrointestinal upset, administration of PRIFTIN with food may be useful. Patients should be instructed to notify their physician promptly of 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.

Compliance with the full course of therapy must be emphasized, and the importance of not missing any doses of the daily administered companion medications in the Intensive Phase must be stressed. (See DOSAGE and ADMINISTRATION and

WARNINGS

Laboratory Test

Adults treated for tuberculosis with rifapentine should have baseline measurements of hepatic enzymes, bilirubin, a complete blood count, and a platelet count (or estimate).

Patients should be seen at least monthly during therapy and should be specifically questioned concerning symptoms associated with adverse reactions. All patients with abnormalities should have follow-up; including laboratory testing, if necessary. Routine laboratory monitoring for toxicity in people with normal baseline measurements is generally not necessary.

Therapeutic concentrations of rifampin have been shown to inhibit standard mocrobiological assays for serum folate and Vitamin B₁₂. Similar drug-laboratory interactions should be considered for rifapentine; thus. Alternative assay methods should be considered.

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