Priftin® is indicated for the treatment of pulmonary tuberculosis caused by Mycobacterium tuberculosis. Priftin 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 (2) and Clinical Studies (14)].
Limitations of Use
Priftin 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 (5.1) and Clinical Studies (14)].
Priftin has not been studied as part of the Initial Phase treatment regimen in HIV seropositive patients with pulmonary tuberculosis.
Priftin should not be used as monotherapy in either the initial or the continuation phases of antituberculous treatment.
Priftin Dosage and Administration
Dosage
Priftin has been studied for the treatment of tuberculosis caused by drug-susceptible organisms as part of regimens consisting of an initial 2 month phase followed by a 4 month continuation phase.
These recommendations apply only to the treatment of patients with drug-susceptible organisms.
Initial Phase (2 Months) of short course treatment for pulmonary tuberculosis:
Priftin should be administered at a dose of 600 mg (4 × 150 mg tablets) twice weekly for two months by direct observation of therapy, with an interval of no less than 3 consecutive days (72 hours) between doses, in combination with other antituberculosis drugs as part of an appropriate regimen which includes daily companion drugs such as ethambutol, pyrazinamide, and streptomycin.
The determination of the companion drugs to be used should be made by the treating physician and depends on the results of susceptibility testing as well as the phase of treatment. Priftin has been studied as part of the initial regimen with isoniazid, pyrazinamide and ethambutol [see Clinical Studies (14)].
Continuation Phase (4 Months) of short course treatment for pulmonary tuberculosis:
Following the Initial Phase (2 months), Continuation Phase (4 months) treatment may consist of Priftin 600 mg once weekly for 4 months in combination with isoniazid or an appropriate antituberculosis agent for susceptible organisms by direct observation therapy.
Priftin was studied as a component of a 4 month continuation phase in conjunction with INH 900 mg once a week in two clinical studies [see Clinical Studies (14)].
The prescribing physician is directed to current guidelines for further direction on other possible components of the Continuation Phase regimen as well as for directions on extending this phase.
Administration
Take Priftin with meals. Administration of rifapentine with a meal increases oral bioavailability and may reduce the incidence of gastrointestinal upset, nausea, and/or vomiting. [see Clinical Pharmacology (12.3)].
In patients with conditions which predispose them to neuropathy (e.g., nutritional deficiency, HIV infection, renal failure, alcoholism, as well as pregnant and breastfeeding women), concomitant administration of pyridoxine (Vitamin B6) is recommended in order to avoid INH-associated peripheral neuropathy (see American Thoracic Society/Centers for Disease Control/Infectious Disease Society of America Guideline for the Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children).
Dosage Forms and Strengths
Priftin is supplied as 150 mg round normal convex dark-pink film-coated tablets debossed "Priftin" on top and "150" on the bottom.
Contraindications
Hypersensitivity
Priftin is contraindicated in patients with a history of hypersensitivity to rifamycins.
Warnings and Precautions
HIV Seropositive Patients
Priftin 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 (14)].
Priftin 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 Priftin 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 (7.1 and 7.2) and Clinical Pharmacology (12.3)]
Relapse of Tuberculosis
Priftin 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 (14)].
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 (17)].
Higher relapse rates have also been seen in HIV positive patients receiving Priftin 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 (14)].
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
Priftin 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
Priftin 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.
Adverse Reactions
Serious and Otherwise Important Adverse Reactions
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
- Hypersensitivity [see Contraindications (4.1)]
- Hepatotoxicity [see Warnings and Precautions (5.4)]
- Hyperbilirubinemia [see Warnings and Precautions (5.5)]
- Discoloration of Body Fluids [see Warnings and Precautions (5.6)]
- Porphyria [see Warnings and Precautions (5.7)]
- Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.8)]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to Priftin in a randomized, open label, active-controlled trial of patients with pulmonary tuberculosis, excluding those with HIV-infection. The population consisted of primarily of male subjects with a mean age of 37 ± 11 years. In the initial 2 month phase of treatment (60 days), 361 patients received rifapentine 600 mg twice a week in combination with daily isoniazid, pyrazinamide, and ethambutol and 361 subjects received rifampin in combination with isoniazid, pyrazinamide and ethambutol all administered daily. Ethambutol was discontinued when drug susceptibly testing was completed. During the 4 month continuation phase, 321 patients in the rifapentine group continued to receive rifapentine 600 mg dosed once weekly with isoniazid and 307 patients in the rifampin arm received twice weekly rifampin and isoniazid. Both treatment groups received pyridoxine (Vitamin B6) over the 6 month treatment period.
Twenty-two deaths occurred in the study (eleven in the rifampin combination therapy group and eleven in the rifapentine combination therapy group).
In the study, 18/361 (5.0%) rifampin combination therapy patients discontinued the study due to an adverse reaction compared to 11/361 (3.0%) rifapentine combination therapy patients. Three patients (two rifampin combination therapy patients and one rifapentine combination therapy patient) were discontinued in the Initial Phase as a result of hepatitis with increased liver function tests (ALT, AST, LDH, and bilirubin). Concomitant medications for all three patients included isoniazid, pyrazinamide, ethambutol, and pyridoxine. The two rifampin patients and one rifapentine patient recovered without sequelae.
As shown in Table 1, hyperuricemia was the most frequently reported reaction and was most likely related to the pyrazinamide since only two cases were reported in the Continuation Phase when this drug was no longer included in the treatment regimen.
Seven patients had adverse reactions associated with an overdose. In the rifampin combination group these reactions included hematuria, anorexia, back pain, arthralgia, and myalgia. In the rifapentine combination group these reactions included hematuria, neutropenia, hyperglycemia, ALT increased, hyperuricemia, pruritus, and arthritis.
The following table (Table 1) presents treatment-emergent adverse reactions associated with the use of any of the four drugs in the regimens (rifapentine/rifampin, isoniazid, pyrazinamide, or ethambutol) which occurred in ≥1% of patients during treatment and post-treatment through the first three months of follow-up.
Table 1. Treatment-Emergent Adverse Reactions Occurring in ≥1% of Patients
|
Initial Phase |
Continuation Phase |
Total |
|---|
| System Organ Class Preferred Term |
Rifapentine Combination (N=361)
N(%) |
Rifampin Combination
(N=361)
N(%) |
Rifapentine Combination (N=304)
N(%) |
Rifampin Combination
(N=317)
N(%) |
Rifapentine Combination
(N=361)
N(%) |
Rifampin Combination
(N=361)
N(%) |
|---|
| Note: ≥1% refers to rifapentine in the TOTAL column. |
|
| RENAL & URINARY |
|
|
|
|
|
|
| Pyuria |
39 (10.8)_ |
56 (15.5) |
47 (14.8) |
36 (11.8) |
78 (21.6) |
83 (23.0) |
| Proteinuria |
36 (10.0) |
53 (14.7) |
14 (4.4) |
27 (8.9) |
47 (13.0) |
71 (19.7) |
| Hematuria |
39 (10.8) |
38 (10.5) |
32 (10.1) |
27 (8.9) |
64 (17.7) |
61 (16.9) |
| Urinary Tract Infection |
32 (8.9) |
24 (6.6) |
23 (7.3) |
10 (3.3) |
48 (13.3) |
32 (8.9) |
| Urinary Casts |
20 (5.5) |
22 (6.1) |
11 (3.5) |
7 (2.3) |
29 (8.0) |
28 (7.8) |
| Cystitis |
5 (1.4) |
6 (1.7) |
1 (0.3) |
1 (0.3) |
6 (1.7) |
7 (1.9) |
| METABOLIC & NUTRITIONAL |
|
|
|
|
|
|
| Hyperuricemia |
115 (31.9) |
83 (23.0) |
0 (0.0) |
2 (0.7) |
115 (31.9) |
83 (23.0) |
| Hyperkalemia |
14 (3.9) |
22 (6.1) |
20 (6.3) |
21 (6.9) |
33 (9.1) |
41 (11.4) |
| Hypoglycemia |
22 (6.1) |
27 (7.5) |
15 (4.7) |
11 (3.6) |
36 (10.0) |
35 (9.7) |
| Nonprotein Nitrogen Increased |
4 (1.1) |
3 (0.8) |
10 (3.2) |
15 (4.9) |
14 (3.9) |
17 (4.7) |
| Hyperglycemia |
10 (2.8) |
8 (2.2) |
4 (1.3) |
2 (0.7) |
13 (3.6) |
9 (2.5) |
| LDH Increased |
5 (1.4) |
7 (1.9) |
0 (0.0) |
2 (0.7) |
5 (1.4) |
9 (2.5) |
| Hyperphosphatemia |
2 (0.6) |
1 (0.3) |
3 (0.9) |
5 (1.6) |
5 (1.4) |
6 (1.7) |
| HEMATOLOGIC |
|
|
|
|
|
|
| Anemia |
41 (11.4) |
41 (11.4) |
5 (1.6) |
10 (3.3) |
44 (12.2) |
51 (14.1) |
| Lymphopenia |
38 (10.5) |
37 (10.2) |
10 (3.2) |
9 (3.0) |
46 (12.7) |
45 (12.5) |
| Neutropenia |
22 (6.1) |
21 (5.8) |
27 (8.5) |
24 (7.9) |
45 (12.5) |
41 (11.4) |
| Leukopenia |
16 (4.4) |
11 (3.0) |
11 (3.5) |
9 (3.0) |
24 (6.6) |
17 (4.7) |
| Leukocytosis |
6 (1.7) |
13 (3.6) |
5 (1.6) |
2 (0.7) |
11 (3.0) |
15 (4.2) |
| Neutrophilia |
5 (1.4) |
11 (3.0) |
4 (1.3) |
2 (0.7) |
9 (2.5) |
13 (3.6) |
| Thrombocytosis |
20 (5.5) |
13 (3.6) |
1 (0.3) |
0 (0.0) |
20 (5.5) |
13 (3.6) |
| Thrombocytopenia |
6 (1.7) |
6 (1.7) |
4 (1.3) |
6 (2.0) |
9 (2.5) |
11 (3.0) |
| Polycythemia |
3 (0.8) |
2 (0.6) |
5 (1.6) |
3 (1.0) |
8 (2.2) |
5 (1.4) |
| Lymphadenopathy |
4 (1.1) |
2 (0.6) |
0 (0.0) |
2 (0.7) |
4 (1.1) |
4 (1.1) |
| BODY AS A WHOLE - GENERAL |
|
|
|
|
|
|
| Back Pain |
15 (4.2) |
11 (3.0) |
11 (3.5) |
4 (1.3) |
25 (6.9) |
15 (4.2) |
| Pain |
14 (3.9) |
17 (4.7) |
8 (2.5) |
5 (1.6) |
22 (6.1) |
22 (6.1) |
| Chest Pain |
10 (2.8) |
11 (3.0) |
10 (3.2) |
5 (1.6) |
20 (5.5) |
16 (4.4) |
| Injury Accident |
5 (1.4) |
5 (1.4) |
12 (3.8) |
14 (4.6) |
17 (4.7) |
17 (4.7) |
| Abdominal Pain |
3 (0.8) |
3 (0.8) |
4 (1.3) |
4 (1.3) |
7 (1.9) |
7 (1.9) |
| Fever |
5 (1.4) |
7 (1.9) |
1 (0.3) |
1 (0.3) |
5 (1.4) |
7 (1.9) |
| Fatigue |
3 (0.8) |
1 (0.3) |
1 (0.3) |
3 (1.0) |
4 (1.1) |
4 (1.1) |
| Edema Dependent |
4 (1.1) |
1 (0.3) |
0 (0.0) |
1 (0.3) |
4 (1.1) |
2 (0.6) |
| DERMATOLOGIC |
|
|
|
|
|
|
| Rash |
15 (4.2) |
26 (7.2) |
8 (2.5) |
8 (2.6) |
22 (6.1) |
33 (9.1) |
| Sweating Increased |
19 (5.3) |
18 (5.0) |
5 (1.6) |
4 (1.3) |
23 (6.4) |
22 (6.1) |
| Pruritus |
10 (2.8) |
16 (4.4) |
3 (0.9) |
0 (0.0) |
13 (3.6) |
16 (4.4) |
| Acne |
9 (2.5) |
5 (1.4) |
0 (0.0) |
3 (1.0) |
9 (2.5) |
8 (2.2) |
| Skin Disorder |
2 (0.6) |
3 (0.8) |
3 (0.9) |
5 (1.6) |
5 (1.4) |
8 (2.2) |
| Rash Maculopapular |
6 (1.7) |
3 (0.8) |
0 (0.0) |
1 (0.3) |
6 (1.7) |
4 (1.1) |
| Eczema |
2 (0.6) |
2 (0.6) |
3 (0.9) |
2 (0.7) |
4 (1.1) |
3 (0.8) |
| RESPIRATORY |
|
|
|
|
|
|
| Hemoptysis |
27 (7.5) |
20 (5.5) |
6 (1.9) |
6 (2.0) |
30 (8.3) |
25 (6.9) |
| Coughing |
21 (5.8) |
8 (2.2) |
9 (2.8) |
11 (3.6) |
29 (8.0) |
17 (4.7) |
| Upper Respiratory Tract Infection |
5 (1.4) |
9 (2.5) |
12 (3.8) |
15 (4.9) |
17 (4.7) |
22 (6.1) |
| Bronchitis |
1 (0.3) |
1 (0.3) |
8 (2.5) |
1 (0.3) |
9 (2.5) |
2 (0.6) |
| Pharyngitis |
5 (1.4) |
0 (0.0) |
2 (0.6) |
5 (1.6) |
7 (1.9) |
5 (1.4) |
| Epistaxis |
2 (0.6) |
2 (0.6) |
3 (0.9) |
1 (0.3) |
5 (1.4) |
3 (0.8) |
| Pleuritis |
4 (1.1) |
1 (0.3) |
0 (0.0) |
1 (0.3) |
4 (1.1) |
2 (0.6) |
| GASTROINTESTINAL |
|
|
|
|
|
|
| Dyspepsia |
6 (1.7) |
11 (3.0) |
4 (1.3) |
6 (2.0) |
10 (2.8) |
17 (4.7) |
| Vomiting |
6 (1.7) |
14 (3.9) |
3 (0.9) |
3 (1.0) |
9 (2.5) |
17 (4.7) |
| Nausea |
7 (1.9) |
3 (0.8) |
2 (0.6) |
1 (0.3) |
9 (2.5) |
4 (1.1) |
| Constipation |
6 (1.7) |
1 (0.3) |
2 (0.6) |
1 (0.3) |
7 (1.9) |
2 (0.6) |
| Diarrhea |
5 (1.4) |
2 (0.6) |
2 (0.6) |
0 (0.0) |
7 (1.9) |
2 (0.6) |
| Hemorrhoids |
4 (1.1) |
0 (0.0) |
1 (0.3) |
0 (0.0) |
5 (1.4) |
0 (0.0) |
| INFECTIOUS DISEASE |
|
|
|
|
|
|
| Influenza |
9 (2.5) |
8 (2.2) |
22 (6.9) |
12 (3.9) |
28 (7.8) |
20 (5.5) |
| Infection Tuberculosis |
0 (0.0) |
5 (1.4) |
9 (2.8) |
4 (1.3) |
9 (2.5) |
9 (2.5) |
| Infection |
1 (0.3) |
2 (0.6) |
4 (1.3) |
4 (1.3) |
5 (1.4) |
6 (1.7) |
| Herpes Zoster |
2 (0.6) |
0 (0.0) |
2 (0.6) |
3 (1.0) |
4 (1.1) |
3 (0.8) |
| HEPATIC & BILIARY |
|
|
|
|
|
|
| ALT Increased |
18 (5.0) |
23 (6.4) |
7 (2.2) |
10 (3.3) |
25 (6.9) |
32 (8.9) |
| AST Increased |
15 (4.2) |
18 (5.0) |
7 (2.2) |
8 (2.6) |
21 (5.8) |
26 (7.2) |
| NEUROLOGIC |
|
|
|
|
|
|
| Headache |
11 (3.0) |
13 (3.6) |
3 (0.9) |
7 (2.3) |
14 (3.9) |
20 (5.5) |
| Dizziness |
5 (1.4) |
5 (1.4) |
1 (0.3) |
1 (0.3) |
6 (1.7) |
6 (1.7) |
| Tremor |
3 (0.8) |
1 (0.3) |
2 (0.6) |
0 (0.0) |
5 (1.4) |
1 (0.3) |
| PSYCHIATRIC |
|
|
|
|
|
|
| Anorexia |
14 (3.9) |
18 (5.0) |
8 (2.5) |
6 (2.0) |
21 (5.8) |
22 (6.1) |
| Insomnia |
2 (0.6) |
2 (0.6) |
2 (0.6) |
2 (0.7) |
4 (1.1) |
4 (1.1) |
| MUSCULOSKELETAL |
|
|
|
|
|
|
| Arthralgia |
13 (3.6) |
13 (3.6) |
3 (0.9) |
5 (1.6) |
16 (4.4) |
18 (5.0) |
| Arthritis |
4 (1.1) |
5 (1.4) |
1 (0.3) |
0 (0.0) |
4 (1.1) |
5 (1.4) |
| Arthrosis |
4 (1.1) |
1 (0.3) |
0 (0.0) |
1 (0.3) |
4 (1.1) |
2 (0.6) |
| Gout |
3 (0.8) |
1 (0.3) |
1 (0.3) |
0 (0.0) |
4 (1.1) |
1 (0.3) |
| CARDIOVASCULAR |
|
|
|
|
|
|
| Hypertension |
3 (0.8) |
5 (1.4) |
3 (0.9) |
2 (0.7) |
6 (1.7) |
7 (1.9) |
| OPHTHALMOLOGIC |
|
|
|
|
|
|
| Conjuctivitis |
8 (2.2) |
2 (0.6) |
1 (0.3) |
1 (0.3) |
9 (2.5) |
3 (0.8) |
In addition to the adverse reactions reported in Table 1, adverse reactions were reported post-treatment during the 3 month through 24 month follow-up period. Although the protocol for this study specified collection of serious adverse reactions during this period, some non-serious adverse reactions were reported as well. For the rifapentine combination group these included the following: hematuria, infection tuberculosis, proteinuria, urinary casts, hyperkalemia, hypoglycemia, injury accident, skin disorder, respiratory disorder, stupor, prostatic disorder.
Treatment-emergent adverse reactions reported during treatment and post-treatment through the first three months of follow-up in <1% of the rifapentine combination therapy patients are presented below by body system in order of frequency.
Renal & Urinary: urethral disorder, dysuria, pyelonephritis, urinary incontinence, urination disorder.
Metabolic & Nutritional: weight decrease, BUN increased, diabetes mellitus, alkaline phosphatase increased, hypophosphatemia, hypercalcemia, hypovolemia, weight increase.
Hematologic: lymphocytosis, hematoma, purpura, anemia hypochromic, anemia normocytic, thrombosis.
Body as a Whole - General: laboratory test abnormal, edema legs, asthenia, edema face, abscess, edema peripheral, malaise.
Dermatologic: skin ulceraction, urticaria, dry skin, furunculosis, skin discoloration, dermatitis fungal, nail disorder, alopecia, rash erythematous.
Respiratory: abnormal breath sounds, pneumothorax, pneumonia, pleural effusion, rhinitis, dyspnea, pneumonitis, sinusitis, sputum increased, pulmonary fibrosis, upper respiratory congestion, asthma, chest x-ray abnormal, bronchospasm, laryngeal edema, laryngitis, respiratory disorder.
Gastrointestinal: tooth disorder, gastroenteritis, gastritis, esophagitis, cheilitis, dry mouth, pancreatitis, proctitis, salivary gland enlargement, tenesmus, gastrointestinal disorder not specified.
Infectious Disease: infection fungal, infection parasitic, infection protozoan.
Hepatic & Biliary: bilirubinemia, hepatomegaly, jaundice.
Neurologic: somnolence, seizure not specified, dysphonia, hypoesthesia, torticollis, hypertonia, hyporeflexia, meningitis, migraine headache, stupor.
Psychiatric: anxiety, confusion, drug abuse, aggressive reaction, agitation.
Musculoskeletal: myalgia, myositis, bone fracture, muscle weakness, muscle spasm.
Cardiovascular: syncope, tachycardia, palpitation, hypotension orthostatic, pericarditis.
Reproductive Disorders: penis disorder, vaginitis, vaginal hemorrhage, cervical smear test positive, leukorrhea, mastitis male, prostatic disorder.
Hearing & Vestibular: ear disorder not specified, otitis media, earache, otitis externa, tympanic membrane perforation.
Ophthalmologic: eye pain, eye abnormality.
Neoplasms: pulmonary carcinoma, neoplasm not specified, carcinoma, lipoma.
Vascular (Extracardiac): thrombophlebitis deep, vascular disorder, vasodilation.
Special Senses Other: taste loss.
Pregnancy, puerperium and perinatal conditions: abortion
In another randomized, open-label trial in 1075 HIV seronegative and seropositive patients with pulmonary tuberculosis the overall adverse event rate did not differ substantially from the previous trial. Patients who had completed an initial 2 month phase of treatment with 4 drugs were randomly assigned to receive either rifapentine 600 mg and isoniazid once weekly or rifampin and isoniazid twice weekly for the 4 month continuation phase.
In the rifapentine arm, 502 HIV seronegative and 36 HIV seropositive patients were randomized and in the rifampin arm 502 HIV seronegative and 35 HIV seropositive patients were randomized to treatment.
The death rate among all study participants was 71/1075 (6.6%) and did not differ between the two treatment groups (6.5% for the rifapentine combination regimen compared to 6.7% for the rifampin combination regimen; P = 0.87).
There were 526 treatment-emergent adverse events regardless of causality reported from 251 patients treated with the rifapentine combination regimen and 513 adverse events reported from 248 patients treated with the rifampin combination regimen. On both study arms the most frequently reported adverse events were hyperglycemia, pneumonia, liver toxicity, and death and were consistent with concurrent underlying conditions that included alcohol abuse, pancreatitis and HIV.
There was a greater percentage of patients in the rifampin combination arm who developed hepatic adverse events (35/513; 6.8 %) compared to 20/526 (3.8%) in the rifapentine combination arm. The types of other adverse events were similar between the treatment arms.
Hyperuricemia was not reported as an adverse reaction in this study of continuation phase therapy. In the previous study which evaluated initial therapy containing pyrazinamide, hyperuricemia was reported in 32% of rifapentine and 23% of rifampin combination treated patients (see Table 1).
Drug Interactions
Protease Inhibitors and Reverse Transcriptase Inhibitors
Rifapentine is an inducer of CYP450 enzymes. Concomitant use of Priftin 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 Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]
Hormonal Contraceptives
Priftin may reduce the effectiveness of hormonal contraceptives. Therefore, patients using oral, transdermal patch, or other systemic hormonal contraceptives should be advised to change to non-hormonal methods of birth control.
Cytochrome P450 3A4 and 2C8/9
Rifapentine is an inducer of cytochromes P4503A4 and P4502C8/9. Therefore, rifapentine may increase the metabolism of other coadministered drugs that are metabolized by these enzymes. Induction of enzyme activities by rifapentine occurred within 4 days after the first dose. Enzyme activities returned to baseline levels 14 days after discontinuing rifapentine. In addition, the magnitude of enzyme induction by rifapentine was dose and dosing frequency dependent; less enzyme induction occurred when 600 mg oral doses of rifapentine were given once every 72 hours versus daily.
In vitro and in vivo enzyme induction studies have suggested rifapentine induction potential may be less than rifampin but more potent than rifabutin.
Rifampin has been reported to accelerate the metabolism and may reduce the activity of the following drugs; hence, rifapentine may also increase the metabolism and decrease the activity of these drugs. Dosage adjustments of the drugs in Table 2 or of other drugs metabolized by cytochrome P4503A4 or P4502C8/9 may be necessary if they are given concurrently with rifapentine.
Table 2. Drug Interactions with Priftin: Dosage Adjustment may be Necess
