Rifapentine

Rifapentine is an antibiotic drug that treats pulmonary tuberculosis (TB). Treatment begins in an intensive phase of twice-weekly dosing, followed by a maintenance phase of once-weekly dosing.

The drug's brand name is Prifkin, and it is marketed by Sanofi-Aventis. It was approved by the Food and Drug Administration in June 1998.

Source

Rifapentine is an antibiotic in the rifampycin family of drugs. These drugs are derived from a fungus called Amycolatopsis mediterranei which originated from a pine forest outside of Nice, France. Rifapentine was originally investigated as a treatment for tuberculosis in the 1980s and 1990s. The molecular formula is

C₄H₂₄N₄O₁₂

The chemical name for rifapentime is rifamycin 3-[{(4-cyclopentyl-l-piperazinyl) imino} methyl]-or 3-[N-(4-Cyclopentyl - l-piperazinylinterminidoyl] rifamycin or 5,6,9,17,19,21 hexahydrom methoxy 2,4,12,16,18,20,22-heptamethyl-8-[N-(4-cyclopentyl-l-piperazinyl)-formimidoyl]-l- (epoxypentadeca[1,11,13]trienimino) naphtho[2,l-b] furan-1,11 (2H)-dione 21-acetate.

Uses/Indications

Transmission electron micrograph of the ultrastructures of the bacteria that cause tuberculosis, Mycobacterium tuberculosis.

How the Body Affects Rifapentine

The concentration of rifapentine in the blood reaches maximum about 5-6 hours after taking a dose. Food increases absorption of rifapentine by approximately 43%.^[2] Rifapentine is metabolized into a form that also has antibiotic activity, and both rifapentine and this compound contribute to the effectiveness of treatment. Most rifapentine is excreted in the feces with a small amount excreted in the urine.

In special populations

One study found that blood concentrations of rifapentine were 20%-30% lower in patients with HIV/AIDS compared to healthy volunteers.^[3] The elimination of rifapentine is similar in adolescents, adults, and the elderly. Moreover, kidney and liver damage have little effect on elimination. Females eliminate rifapentine from the body more slowly than do males, but whether this makes any difference to the effectiveness of the treatment is not known.

Side Effects

These side effects require immediate attention from a physician:

• Loss of appetite
• Fever
• Dark color of urine
• Feeling of general discomfort
• Nausea or vomiting
• Yellow skin or eyes
• Pain or swelling in the joints

If severe or constant diarrhea develops, the patient should contact a physician immediately.

Because rifapentine is taken with other medications, the following list of side effects may be shared with any of the other drugs used for the treatment of tuberculosis:

• Blood in urine
• Itchiness
• Loss of iron in the body
• Loss of appetite
• Skin breakouts
• Rash
• Nausea and vomiting
• Pain, including joint pain

Rifapentine can change the color of some body fluids such as the saliva, urine, breast milk, tears, and sweat to an orange-red. The skin, teeth, and tongue may also change color. Dentures and contact lenses can be permanently stained.

Risks and Precautions

Rifapentine should not be taken by patients who are allergic to any medications in the rifampycin family such as rifampin (Rifadin, Rimactane) or have a history of the disease porphyria.

Rifapentine must be taken according to instructions in order to be successful. Relapse of tuberculosis is more likely if a dose is missed.

Antituberculosis drugs can harm the liver. Rifapentine should be used in patients with abnormal liver function only with extreme caution and with intensive monitoring for adverse events. Liver tests are often performed in these patients to monitor the health of the liver.

Rifapentine can cause postnatal bleeding of both the mother and child when given during the last few weeks of pregnancy. Vitamin K is often given to help prevent bleeding. Tests can be performed to determine the risk of bleeding during pregnancy. Rifapentine should only be used if the benefits of treatment outweigh the risks. Whether nursing infants are exposed to rifapentine in breast milk is not known. Nursing mothers may want to cease breast-feeding their infants during treatment, or treatment with rifapentine may be stopped in nursing mothers.

Rifapentine may increase the metabolism of several other drugs.

People with poor nutrition, diabetes, a history of alcoholism, or who are teenagers may be given vitamin B6 supplements while taking rifapentine.

Drug Interactions

Rifapentine increases the activity of enzymes that metabolize (break down) drugs. Therefore, it has the potential to interact with several other drugs. Priftin increases the metabolism of drugs used to treat HIV/AIDS called protease inhibitors. Some of these inhibitors include ritonavir (Norvir) and indinavir (Crixivan). An interaction between rifapentine and indinavir has been reported.^[4] In that case, rifapentine (600 mg) was given twice a week for 14 days followed by treatment with indinavir (800 mg) given three times daily for 14 days. Rifapentine reduced blood concentrations of indinavir by 70% and increased its elimination from the body by 300%.

Rifapentine may interact with several other classes of drugs, including the following:

• Anticonvulsants; e.g., phenytoin (Dilantin)
• Antipsychotics e.g., haloperidol (Haldol)
• Antiarrhythmics; e.g., mexilitine (Mexitil)
• Calcium channel blockers; e.g., verapamil (Cordilox), nifedipine (Adalat)
• Beta-blockers; e.g., propranolol (Inderal)
• Antibiotics; e.g., ciprofloxacin (Ciprinol), chloramphenicol (Chloromycetin)
• Anticoagulants; e.g., warfarin (Coumadin)
• Antifungals; e.g., ketoconazole (Nizarol), itraconazole (Sporanox)
• Benzodiazepines: e.g., diazepam (Valium)
• Cardiac glycosides e.g., digoxin (Lanoxin)
• Imunosuppressants; e.g., cyclosporine (Neoral)
• Antidiabetics; e.g., metformin (Glucophage)

Rifapentine may reduce the effectiveness of birth control pills. Other forms of contraception should be used during treatment with rifapentine.

Alternatives

Rifapentine is an alternative to rifampin or rifabutin in pulmonary tuberculosis treatment regimens. The major advantage of rifapentine is that is taken once a week, after the initial phase of treatment. Rifampin must be taken more often. This is an important consideration as adherence to a drug regimen by a patient if often incomplete in the treatment of tuberculosis. Nonadherence to the antituberculosis treatment regimen is well known to be the most common cause of treatment failure, relapse, and the emergence of drug resistance, including multi-drug resistant TB.

Rifapentine and rifampin have the same mode of action and similar efficacy and side effect profiles.

In high-risk TB patients — HIV positive; those with cavitary lesions or extrapulmonary involvement — rifapentine is not recommended because isoniazid plus rifapentine is inferior to standard twice-weekly therapy with isoniazid plus rifampin. Recent studies have suggested that the substitution of moxifloxacin, a quinolone antibiotic, for isoniazid and an increase in the dose of rifapentine could improve the efficacy of once-weekly regimens and reduce treatment failure rates.^[5]

Clinical Trials

A study conducted in Canada and the United States compared once-weekly administration of rifapentine plus isoniazid or rifampicin plus isoniazid twice a week in HIV-negative patients.^[6] After two months, 9.2% and 5.6% of rifapentine- and rifampicin-treated patients, respectively, failed to respond to treatment, or had relapse of tuberculosis.

Rifapentine can cause the emergence of tuberculosis strains that are resistant to treatment, especially in patients with HIV/AIDS. One study found that resistance to rifapentine developed in four out of five patients with HIV/AIDS in whom tuberculosis had relapsed.^[7]

References

1. ↑ American Thoracic Society, CDC, and Infectious Diseases Society of America: Treatment of Tuberculosis
2. ↑ Keung AC, Owens RC Jr, Eller MG, et al. Pharmacokinetics of rifapentine in subjects seropositive for the human immunodeficiency virus: a phase I study. Antimicrob Agents Chemother 1999;43:1230-3.
3. ↑ Keung AC, Owens RC Jr, Eller MG, et al. Pharmacokinetics of rifapentine in subjects seropositive for the human immunodeficiency virus: a phase I study. Antimicrob Agents Chemother 1999;43:1230-3.
4. ↑ Sanofi-Aventis. Product Information; Available as PDF.
5. ↑ Ian M. Rosenthal, Kathy Williams, Sandeep Tyagi, Andrew A. Vernon, Charles A. Peloquin, William R. Bishai, Jacques H. Grosset, and Eric L. Nuermberger. Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis. Am. J. Respir. Crit. Care Med. 172: 1457-1462. First published online as doi:10.1164/rccm.200507-1072OC
6. ↑ Benator D, Bhattacharya M, Bozeman L, Burman W, Cantazaro A, Chaisson R, Gordin F, Horsburgh CR, Horton J, Khan A, Lahart C, Metchock B, Pachucki C, Stanton L, Vernon A, Villarino ME, Wang YC, Weiner M, Weis S; Tuberculosis Trials Consortium. Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: a randomised clinical trial. Abstract. Lancet. 2002 Aug 17;360(9332):528-34.
7. ↑ Vernon A, Burman W, Benator D, et al. Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid. Abstract. Tuberculosis Trials Consortium. Lancet 1999;353:1843-7.

External Links

• Drugs.com: Priftin Drug Interactions
• Priftin Resource Site: Priftin
• Emedicine: Tuberculosis
• American Thoracic Society, CDC, and Infectious Diseases Society of America: Treatment of Tuberculosis