Priftin

Generic Name: Rifapentine
Class: Antituberculosis Agents
VA Class: AM500
Chemical Name: 3-[[(4-Cyclopentyl-1-piperazinyl)imino]methyl]-rifamycin
Molecular Formula: C47H64N4O12
CAS Number: 61379-65-5

Introduction

Antituberculosis agent; semisynthetic cyclopentylpiperazinyl derivative of rifamycin SV.1 11 12 13

Uses for Priftin

Tuberculosis

Treatment of active (clinical) tuberculosis (TB) in conjunction with other antituberculosis agents.1 4 14 19

For treatment of pulmonary TB, manufacturer states rifapentine can be used in both initial and continuation phases;1 ATC, CDC, and IDSA suggest the drug not be used in the initial phase, but consider the drug a first-line antituberculosis agent for the continuation phase of intermittent regimens used for treatment of pulmonary TB.14

ATS, CDC, and IDSA state that rifapentine can be used in conjunction with isoniazid in the continuation phase in HIV-seronegative patients with noncavity pulmonary TB caused by susceptible Mycobacterium tuberculosis; rifapentine is an alternative to rifampin for use in conjunction with isoniazid in the continuation phase.14

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Experience in HIV-infected patients is limited;1 21 higher rate of TB relapse reported in HIV-infected patients receiving once-weekly regimens of rifapentine and isoniazid.1 14 19 ATS, CDC, IDSA, and other experts state that once-weekly regimens of rifapentine and isoniazid should not be used in HIV-infected patients.14 21 a

Because of limited experience, ATS, CDC, and IDSA state that rifapentine should not be used for treatment of extrapulmonary TB.14

For initial treatment of active TB caused by drug-susceptible M. tuberculosis, recommended multiple-drug regimens consist of an initial intensive phase (2 months) and a continuation phase (4 or 7 months).14 Although the usual duration of treatment for drug-susceptible pulmonary and extrapulmonary TB (except disseminated infections and TB meningitis) is 6–9 months,14 ATS, CDC, and IDSA state that completion of treatment is determined more accurately by the total number of doses and should not be based solely on the duration of therapy.14 A longer duration of treatment (e.g., 12–24 months) usually is necessary for infections caused by drug-resistant M. tuberculosis.14

Patients with treatment failure or drug-resistant M. tuberculosis, including multidrug-resistant (MDR) TB (resistant to both isoniazid and rifampin) or extensively drug-resistant (XDR) TB (resistant to both isoniazid and rifampin and also resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial such as capreomycin, kanamycin, or amikacin), should be referred to or managed in consultation with experts in the treatment of TB as identified by local or state health departments or CDC.14

Priftin Dosage and Administration

Administration

Oral Administration

Administer orally.1

Administration with food may decrease nausea, vomiting, or GI upset in susceptible individuals.1

Manufacturer recommends concomitant administration of pyridoxine (vitamin B6) in those who are malnourished or predisposed to neuropathy (e.g., alcoholics, diabetics), and in adolescents.1

Dosage

Must be used in conjunction with other antituberculosis agents for the treatment of active (clinical) TB.1 14

Used in intermittent (once or twice weekly) multiple-drug TB regimens; manufacturer recommends an interval of ≥3 days (≥72 hours) between doses.1

Pediatric Patients

Tuberculosis
Treatment of Active (Clinical) Tuberculosis
Oral

Children 12–15 years of age: 600 mg twice weekly in the initial intensive treatment phase (2 months), then 600 mg once weekly in the continuation treatment phase (4 months) recommended by manufacturer.1

Adolescents ≥15 years of age: 10 mg/kg (up to 600 mg) once weekly recommended by ATS, CDC, and IDSA for the continuation phase;14 these experts do not recommend use in the intensive phase.14 Duration of the continuation phase is 4 months in those with negative sputum smears at completion of the initial phase or 7 months in those with positive sputum smears at completion of the initial phase.14

Adults

Tuberculosis
Treatment of Active (Clinical) Tuberculosis
Oral

600 mg twice weekly in the initial intensive treatment phase (2 months), then 600 mg once weekly in the continuation treatment phase (4 months) recommended by manufacturer.1

10 mg/kg (up to 600 mg) once weekly recommended by ATS, CDC, and IDSA for the continuation phase;14 these experts do not recommend use in the intensive phase.14 Duration of the continuation phase is 4 months in those with negative sputum smears at completion of the initial phase or 7 months in those with positive sputum smears at completion of the initial phase.14

Prescribing Limits

Pediatric Patients

Tuberculosis
Treatment of Active (Clinical) Tuberculosis
Oral

Maximum 600 mg per dose in once- or twice-weekly regimens.14

Adults

Tuberculosis
Treatment of Active (Clinical) Tuberculosis
Oral

Maximum 600 mg per dose in once- or twice-weekly regimens.14

Special Populations

Hepatic Impairment

No specific dosage recommendations provided by manufacturer;1 dosage adjustments probably not necessary.9

Renal Impairment

No specific dosage recommendations provided by manufacturer.1

Geriatric Patients

Select dosage with caution.1 (See Geriatric Use under Cautions.)

Cautions for Priftin

Contraindications

  • Known hypersensitivity to rifapentine, other rifamycins (rifabutin, rifampin), or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Hepatic Effects

Serious hepatic events reported with rifamycins.1

Use rifapentine in patients with abnormal liver function tests and/or liver disease only when such use is considered necessary and only with caution and close medical supervision.1 (See Hepatic Impairment under Cautions.) Discontinue the drug if signs of liver disease develop or worsen.1 Consider hepatotoxicity profile of other antituberculosis agents (e.g., isoniazid, pyrazinamide) if these drugs are used with rifapentine.1

Hyperbilirubinemia (resulting from competition between rifapentine and bilirubin for excretory pathways in the liver) possible; such competition has been reported between rifampin and bilirubin.1 An isolated report of moderate increase in bilirubin and/or transaminase concentrations is not an indication to interrupt rifapentine therapy; the decision to discontinue therapy should be made after repeating the tests, noting trends in the concentrations, and considering the patient’s clinical condition.1

Clostridium difficile-associated Diarrhea and Colitis

Treatment with anti-infectives, including rifamycins, may permit overgrowth of clostridia.1 17 Consider C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) if diarrhea develops and manage accordingly.1 24 25 26 27 28

Some mild cases of CDAD may respond to discontinuance alone.24 25 26 27 28 Manage moderate to severe cases with fluid, electrolyte, and protein supplements; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.1 24 25 26 27 28 Agents inhibiting peristalsis contraindicated in these patients.1 24 25 26

Interactions

Concomitant use with HIV protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), or certain HIV entry inhibitors not recommended.1 a (See Specific Drugs and Laboratory Tests under Interactions.)

General Precautions

Precautions Related to Treatment of Tuberculosis

Should not be used alone for treatment of active TB; must be used in conjunction with other antituberculosis agents.1 14

Clinical specimens for microscopic examination and mycobacterial cultures and in vitro susceptibility testing should be obtained prior to initiation of antituberculosis therapy and periodically during treatment to monitor therapeutic response.1 14 The antituberculosis regimen should be modified as needed.1 14 Patients with positive cultures after 4 months of treatment should be considered to have failed treatment (usually as the result of noncompliance or drug-resistant TB).14

Compliance with the full course of antituberculosis therapy and all drugs included in the multiple-drug regimen is critical.1 14 Missed doses increase the risk of treatment failure and increase the risk that M. tuberculosis will develop resistance to the antituberculosis regimen.1 14

To ensure compliance, ATS, CDC, and IDSA recommend that directly observed (supervised) therapy (DOT) be used for treatment of active (clinical) TB whenever possible, especially when intermittent regimens are used, when the patient is immunocompromised or infected with HIV, or when drug-resistant M. tuberculosis is involved.14

Patients with Porphyria

Should not be used in patients with porphyria.1

There have been isolated reports of exacerbation of porphyria in patients receiving rifampin (rifampin has enzyme-inducing properties, including induction of delta amino levulinic acid synthetase); similar effects may occur with rifapentine.1

Discoloration of Body Tissues or Fluids

Urine, sweat, sputum, tears, and breast milk may have a red-orange coloration during rifapentine therapy.1 Soft contact lenses and dentures may become permanently stained.1

Patient Monitoring

Obtain baseline measurements of liver function (hepatic enzymes, bilirubin) and hematologic status (CBC, platelet count).1 Routine laboratory monitoring for drug-induced toxicity generally not necessary in patients with normal baseline test results.1

Evaluate patient at least once monthly during therapy; question patient about symptoms associated with adverse effects.1 All patients with abnormalities should be followed up, including laboratory monitoring if indicated.1

Specific Populations

Pregnancy

Category C.1

Rifampin administration during the last few weeks of pregnancy can cause postnatal hemorrhages in the mother and infant that require treatment with vitamin K.1 Similar effects may occur with rifapentine; appropriate clotting parameters should be evaluated if use of rifapentine is considered necessary during the last few weeks of pregnancy.1

ATS, CDC, and IDSA state data are insufficient to recommend use of rifapentine in pregnant women.14

Lactation

Not known whether rifapentine is distributed into milk; discontinue nursing or the drug.1

Breast milk may have a red-orange coloration during rifapentine therapy.1 (See Discoloration of Body Tissues or Fluids under Cautions.)

Pediatric Use

Safety and efficacy not established in children <12 years of age.1 14 Limited pharmacokinetic data available in children 12–15 years of age.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Select dosage with caution, starting at the low end of the dosage range, because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1

Hepatic Impairment

Use in patients with impaired liver function only when clearly necessary and only under strict medical supervision.1 Monitor liver function (especially serum transaminase concentrations) before initiating therapy and every 2–4 weeks during therapy.1 Discontinue if signs of liver disease worsen.1

Common Adverse Effects

Neutropenia, increased AST/ALT, pyuria.1

Interactions for Priftin

Induces CYP3A4 and CYP2C8/9.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs metabolized by CYP3A4 or CYP2C8/9; increased metabolism of these drugs.1

Induces hepatic enzymes to a lesser extent than rifampin and to a greater extent than rifabutin.1

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

β-Adrenergic blocking agents

Potential increased metabolism of the β-adrenergic blocking agent1

Dosage adjustment of the β-adrenergic blocking agent may be needed1

Antacids

In clinical studies, patients were advised to take rifapentine 1 hour before or 2 hours after antacids1

Antiarrhythmic agents (disopyramide, mexiletine, quinidine, tocainide)

Potential increased metabolism of the antiarrhythmic agent1

Dosage adjustment of the antiarrhythmic agent may be needed1

Anticoagulants, oral (warfarin)

Potential increased warfarin metabolism1

Adjustment of warfarin dosage may be needed1

Anticonvulsants (phenytoin)

Potential increased phenytoin metabolism1

Adjustment of phenytoin dosage may be needed1

Antifungals, azoles (fluconazole, itraconazole, ketoconazole)

Potential increased metabolism of the antifungal1

Adjustment of antifungal dosage may be needed1

Antiretrovirals, HIV entry inhibitors

Maraviroc: Concomitant use not recommended

Antiretrovirals, HIV protease inhibitors (PIs)

Indinavir: Decreased AUC and concentrations of indinavir; no effect on pharmacokinetics of rifapentine1

Atazanavir, fosamprenavir, lopinavir, nelfinavir, ritonavir, saquinavir: Potential decreased concentrations of the PI1

Concomitant use with PIs not recommended1 14 a

Manufacturer of rifapentine states use with extreme caution, if at all, in patients receiving PIs1

Antiretrovirals, nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Delavirdine: Potential increased metabolism of the NNRTI1

Delavirdine, efavirenz, nevirapine: HIV-infected patients receiving a NNRTI who are receiving rifapentine for TB may have a higher rate of TB relapse than those treated with other rifamycin-based regimensa

Concomitant use with NNRTIs not recommended14 a

Antiretrovirals, nucleoside reverse transcriptase inhibitors (NRTIs)

Zidovudine: Potential increased metabolism of the NRTI1

Zidovudine: Dosage adjustment of the NRTI may be needed1

Barbiturates

Potential increased metabolism of the barbiturate1

Adjustment of barbiturate dosage may be needed1

Benzodiazepines (e.g., diazepam)

Potential increased metabolism of the benzodiazepine1

Dosage adjustment of the benzodiazepine may be needed1

Calcium-channel blocking agents (diltiazem, nifedipine, verapamil)

Potential increased metabolism of the calcium-channel blocking agent1

Dosage adjustment of the calcium-channel blocking agent may be needed1

Cardiac glycosides

Potential increased metabolism of the cardiac glycoside1

Dosage adjustment of the cardiac glycoside may be needed1

Chloramphenicol

Potential increased metabolism of chloramphenicol1

Dosage adjustment of chloramphenicol may be needed1

Clofibrate

Potential increased metabolism of clofibrate1

Dosage adjustment of clofibrate may be needed1

Corticosteroids

Potential increased metabolism of the corticosteroid1

Dosage adjustment of the corticosteroid may be needed1

Dapsone

Potential increased metabolism of dapsone 1

Dosage adjustment of dapsone may be needed1

Doxycycline

Potential increased metabolism of doxycycline 1

Dosage adjustment of doxycycline may be needed1

Erlotinib

Possible decreased erlotinib AUCb

Avoid concomitant use if possibleb

Fluoroquinolones (e.g., ciprofloxacin)

Potential increased metabolism of ciprofloxacin1

Dosage adjustment of the fluoroquinolone may be needed1

Estrogens/Progestins

Hormonal contraceptives (oral or other systemic): Potential interaction with oral or other systemic hormonal contraceptives1

Use nonhormonal methods of contraception1

Immunosuppressive agents (cyclosporine, tacrolimus)

Potential increased metabolism of the immunosuppressive agent1

Dosage adjustment of the immunosuppressive agent may be needed1

Levothyroxine

Potential increased levothyroxine metabolism1

Dosage adjustment of levothyroxine may be needed1

Macrolides (clarithromycin)

Potential increased clarithromycin metabolism1

Dosage adjustment of clarithromycin may be needed1

Opiate agonists (methadone)

Potential increased metabolism of methadone1

Dosage adjustment of methadone may be needed1

Psychotherapeutic agents (amitriptyline, haloperidol, nortriptyline)

Potential increased metabolism of the psychotherapeutic agent1

Dosage adjustment of the psychotherapeutic agent may be needed1

Quinine

Potential increased metabolism of quinine1

Dosage adjustment of quinine may be needed1

Sildenafil

Potential increased sildenafil metabolism1

Dosage adjustment of sildenafil may be needed1

Sulfonylurea antidiabetic agents

Potential increased metabolism of the sulfonylurea agent1

Dosage adjustment of the antidiabetic agent may be needed1

Theophylline

Potential increased metabolism of theophylline1

Dosage adjustment of theophylline may be needed1

Tests for serum folate and vitamin B12

Standard microbiologic assays for serum folate and vitamin B12 are inhibited by therapeutic rifampin concentrations; similar effects may occur with rifapentine1

Consider using alternative assays to determine serum folate and vitamin B121

Priftin Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from the GI tract; peak plasma concentrations achieved within 5–6 hours.1 Steady-state concentrations achieved by day 10 when a once-daily regimen is used.1

Food

Food increases extent of absorption.1

Compared with administration in the fasting state, AUC increased 43% and peak plasma concentrations increased 44% when a single 600-mg dose was administered with a meal (850 calories, 33 g protein, 55 g fat, 58 g carbohydrate).1

Distribution

Extent

Accumulates in human monocyte-derived macrophages; intracellular concentrations higher than extracellular concentrations.1

Plasma Protein Binding

Rifapentine: 97.7%.1

Active metabolite (25-desacetyl rifapentine): 93.2%.1

Special Populations

Plasma protein binding not influenced by hepatic impairment.1

Elimination

Metabolism

Metabolized by esterase enzymes to 25-desacetyl rifapentine; metabolite is active against mycobacteria.1 Rifapentine does not induce its own metabolism.1

Elimination Route

Excreted in feces (70%) and urine (17%).1

Half-life

Rifapentine: 13.19 hours.1

25-desacetyl rifapentine: 13.35 hours.1

Special Populations

Clinical importance of impaired hepatic function on disposition of rifapentine and its major metabolite not known.1 AUC may be slightly higher and the half-life prolonged in patients with hepatic impairment, but accumulation is not expected to occur.9

Pharmacokinetics not evaluated to date in patients with renal impairment.1 Only 17% of a dose eliminated in urine.1

Pharmacokinetics in geriatric individuals similar to that reported in younger adults.1

Pharmacokinetics in adolescents 12–15 years of age weighing <45 kg who received rifapentine 450 mg and in those weighing ≥45 kg who received 600 mg were similar to those reported in adults.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C); protect from excessive heat and humidity.1

Actions and Spectrum

  • A cyclopentyl rifamycin structurally and pharmacologically similar to other rifamycins (rifampin, rifabutin).1 2 3 5 14

  • Usually bactericidal in action.1

  • Inhibits DNA-dependent RNA polymerases in susceptible Mycobacterium tuberculosis.1 Both rifapentine and its major metabolite have antimicrobial activity.1

  • Mycobacterium: Active in vitro and in clinical infections against M. tuberculosis.1 2 3 5 19 20 Has some activity against M. avium complex (MAC);5 19 clinical relevance unclear.1

  • Gram-negative bacteria: Active in vitro against Brucella,13 Legionella,7 Neisseria,20 Haemophilus influenza,20 Bordetella pertussis, and B. parapertussis.6

  • Gram-positive bacteria: Active in vitro against streptococci,20 staphylococci,20 Corynebacterium pseudodiphtheriticum, Arcanobacterium haemolyticum (formerly Corynebacterium haemolyticum), A. pyogenes, Listeria, Turicella otitidis, Brevibacterium, and Oerskovia.8

  • Natural and acquired resistance to rifapentine reported in vitro and in vivo in strains of M. tuberculosis.1 3 4

  • Cross-resistance occurs between rifapentine and other rifamycins (rifampin, rifabutin).1 3 4 14 M. tuberculosis resistant to rifampin usually are resistant to both rifabutin and rifapentine.14 Cross-resistance does not appear to occur between rifapentine and other antituberculosis agents (e.g., isoniazid, streptomycin).1

Advice to Patients

  • Advise patients that poor compliance with antituberculosis regimens can result in treatment failure and development of drug-resistant TB, which can be life-threatening and lead to other serious health risks.1 14

  • Importance of completing full course of therapy; importance of not missing any doses.1

  • Advise patients likely to experience nausea, vomiting, or GI upset to take rifapentine with food.1

  • Advise patient that rifapentine may impart a red-orange color to urine, sweat, sputum, tears, and breast milk.1 Soft contact lenses and dentures may become permanently stained.1

  • Importance of informing clinicians if fever, loss of appetite, malaise, nausea, vomiting, darkened urine, yellow discoloration of the skin or eyes, or pain or swelling of the joints occurs.1

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Advise patient that reliability of oral or other systemic hormonal contraceptives may be affected; alternative contraceptives should be considered.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Rifapentine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

150 mg

Priftin (with propylene glycol)

Sanofi-Aventis

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Sanofi-Aventis. Priftin (rifapentine) 150 mg tablets prescribing information. Bridgewater, NJ; 2006 Dec.

2. Mor N, Simon B, Mezo N et al. Comparison of activities of rifapentine and rifampin against Myocobacterium tuberculosis residing in human macrophages. Antimicrob Agents Chemother. 1995; 39:2073-7. [IDIS 353843] [PubMed 8540718]

3. Moghazeh SL, Pan XI, Arain T et al. Comparative antimycobacterial activities of rifampin, rifapentine, and KRM-1648 against a collection of rifampin-resistant Mycobacterium tuberculosis isolates with a known rpoB mutations. Antimicrobial Agents cehmother. 1996; 40: 2655-7.

4. Tam CM, Chan SL, Lam CW et al. Rifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis. Am J Respir Crit Care Med. 1998; 157: 1726-33. [IDIS 408910] [PubMed 9620898]

5. Heifets LB, Lindholm-Levy J, Flory MA. Bactericidal activity in vitro of various rifamycins against Myocbacterium avium and Mycobacterium tuberculosis. Am Rev Respir Dise. 1990; 141:626-30.

6. Hoppe JE, Bryskier A. In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to two ketolides (HMR 3004 and HMR 3647), four macrolides (azithromycin, clarithromycin, erythromycinA, and roxithromycin), and two ansamycins (rifampin and rifapentine). Antimicrob Agents Chemother. 1998; 42:965-6. [IDIS 403757] [PubMed 9559823]

7. Schulin T, Wennersten CB, Ferraro MJ et al. Susceptibilities of Legionella spp. to newer antimicrobials in vitro. Antimicrob Agents Chemother. 1998; 42:1520-3. [PubMed 9624509]

8. Soriano F, Fernandez-Roblas R, Calvo R et al. In vitro susceptibilities of aerobic and facultative non-spore-forming gram-positive bacilli to HMR 3647 (RU 66647) and 14 other antimicrobials. Antimicrob Agents Chemother. 1998; 42:1028-33. [PubMed 9593121]

9. Keung ACF, Eller MG, Weir SJ. Pharmacokinetics of rifapentine in patients with varying degrees of hepatic dysfunction. J Clin Pharmacol. 1998; 38: 517-24.

10. Keung ACF, Miller TD, Green VI et al. Bioavailability (BA) and food effects study of rifapentine in healthy adults. Pharm Res. 1995; 12(suppl):S419.

11. Reith K, Keung A, Toren PC et al. Disposition and metabolism of 14C-rifapentine in healthy volunteers. Drug Metab Dispos. 1998; 26:732-8. [IDIS 412479] [PubMed 9698286]

12. Durand DV, Hampden C, Boobis AR et al. Induction of mixed function oxidase activity in man by rifapentine (MDL 473), a long-acting rifamycin derivative. Br J Clin Pharmac. 1986; 21:1-7.

13. Garcia-Rodriguez JA, Munoz-Bellido JL, Fresnadillo MJ et al. In vitro activities of new macrolides and rifapentine against Brucella spp. Antimicrobial Agents and Chemother. 1993; 37:911-3.

14. Centers for Disease Control and Prevention. Treatment of tuberculosis, American Thoracic Society, CDC, and Infectious Diseases Society of America. MMWR Recomm Rep. 2003; 52(RR-11):1-77.

15. US Centers for Disease Control and Prevention. Initial therapy for tuberculosis in the era of multidrug resistance. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Recomm Rep. 1993; 42(RR-7):1-8.

16. Bolan G, Laurie RE, Broome CV. Red man syndrome: inadvertent administration of an excessive dose of rifampin to children in a day-care center. Pediatrics. 1986; 77:633-5. [IDIS 215197] [PubMed 3486402]

17. Hoechst Marion Roussel. Rifadin (rifampin capsules) and Rifadin I.V. (rifampin for injection) prescribing information (dated 1995 May). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:1276-8.

18. Centers for Disease Control. Clinical update: impact of HIV protease inhibitors on the treatment of HIV-infected tuberculosis patients with rifampin. MMWR Morb Mortal Wkly Rep. 1996; 45:921-5. [IDIS 374018] [PubMed 8927017]

19. Jarvis B, Lamb HM. Rifapentine. Drugs. 1998; 56:607-16. [PubMed 9806107]

20. Felmingham D, Robbins MJ, Clark S et al. The in vitro activity of rifampicin and rifapentine against recent clinical bacterial isolates. Abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Washington, DC: American Society for Microbiology. 1997:152. Abstract No. F-35.

21. Centers for Disease Control and Prevention. Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations. MMWR Recomm Rep. 1998; 47(RR-20):1-58.

22. Tam CM. Rifapentine: a viewpoint. Drugs. 1998; 56:617.

23. Chaulet P. Rifapentine: a viewpoint. Drugs. 1998; 56:617.

24. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis. 1998; 26:1027-36. [IDIS 407733] [PubMed 9597221]

25. Gerding DN, Johnson S, Peterson LR et al for the Society for Healthcare Epidemiology of American. Position paper on Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995; 16:459-77. [PubMed 7594392]

26. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50 (IDIS 386628) [IDIS 386628] [PubMed 9149180]

27. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11. [IDIS 407213] [PubMed 9659970]

28. Wilcox MH. Treatment of Clostridium difficile infection. J Antimicrob Chemother. 1998; 41(Suppl C):41-6. [IDIS 407246] [PubMed 9630373]

29. Food and Drug Administration. Priftin (rifapentine) tablets [October 20, 2000: Aventis]. MedWatch drug labeling changes. Rockville, MD; October 2000. From FDA website ().

31. Aventis Pharmaceuticals, Kansas City, MO: Personal communication.

a. Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (December 1, 2007). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website ().

b. Genentech. Tarceva (erlotinib) tablets prescribing information. South San Francisco, CA; 2007 Mar.

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