Rifapentine warnings and precautions

Rifapentine
FDA Package Insert (PRIFTIN®)
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Overdosage
Dosage and Administration
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]

Warnings And Precautions

HIV Seropositive Patients

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 Clinical Studies]. Rifapentine has not been studied as part of the Initial Phase treatment regimen in HIV seropositive patients with pulmonary tuberculosis.

Protease Inhibitors and Reverse Transcriptase Inhibitors

Rifapentine is an inducer of CYP450 enzymes. Concomitant use of Rifapentine with other drugs metabolized by these enzymes, such as protease inhibitors and 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 Drug Interactions and Clinical Pharmacology]

Relapse of Tuberculosis

Rifapentine should be used cautiously in subjects with cavitary pulmonary lesions and/or positive sputum cultures after the initial phase of treatment or in those with evidence of bilateral pulmonary disease due to higher rates of relapse. [see Clinical Studies].

Poor compliance with the dosage regimen, particularly during the initial phase in the companion antituberculosis drugs administered with rifapentine, is associated with late sputum conversion and a high relapse rate. Therefore, compliance with the full course of therapy must be emphasized, and the importance of not missing any doses must be stressed [see Patient Counseling Information].

Higher relapse rates have also been seen in HIV positive patients receiving Rifapentine during the continuation phase. Risk factors for relapse included the presence of both pulmonary and extrapulmonary disease at baseline, low CD4 counts, use of azole antifungals and age (younger) [see Clinical Studies].

Hepatotoxicity

Since antituberculous multidrug treatments, 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, rifapentine should be discontinued. Hepatotoxicity of other antituberculosis drugs (eg, isoniazid, pyrazinamide) used in combination with rifapentine should also be taken into account.

Hyperbilirubinemia

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 patient's clinical condition.

Discoloration of Body Fluids

Rifapentine may produce a predominately red-orange discoloration of body tissues and/or fluids (eg, skin, teeth, tongue, urine, feces, saliva, sputum, tears, sweat, and cerebrospinal fluid).

Contact lenses or dentures may become permanently stained.

Porphyria

Rifapentine should not be used in patients with porphyria. Rifampin has enzyme-inducing properties, including induction of delta amino levulinic acid synthetase. Isolated reports have associated porphyria exacerbation with rifampin administration. Based on these isolated reports with rifampin, it may be assumed that rifapentine has a similar effect.

Clostridium difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including the rifamycins, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to 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 antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

References

Adapted from the FDA Package Insert.