Rifapentine, sold under the brand name Priftin, is an

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

used in the treatment of

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

. In active tuberculosis it is used together with other

antituberculosis medication Management of tuberculosis refers to techniques and procedures utilized for treating tuberculosis (TB), or simply a treatment plan for TB. The medical standard for active TB is a short course treatment involving a combination of isoniazid, rifa ...

s. In latent tuberculosis it is typically used with

isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis, it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. F ...

. It is taken by mouth. Common side effects include low neutrophil counts in the blood,

elevated liver enzymes In medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injur ...

, and white blood cells in the urine. Serious side effects may include

liver problems Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...

or ''Clostridioides difficile'' associated diarrhea. It is unclear if use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

is safe. Rifapentine is in the

rifamycin The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium '' Amycolatopsis rifamycinica'' or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective aga ...

family of medication and works by blocking

DNA-dependent RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template. Using the en ...

. Rifapentine was approved for medical use in the United States in 1998. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Medical uses

A systematic review of regimens for prevention of active tuberculosis in HIV-negative individuals with latent TB found that a weekly, directly observed regimen of rifapentine with isoniazid for three months was as effective as a daily, self-administered regimen of isoniazid for nine months. The three-month rifapentine-isoniazid regimen had higher rates of treatment completion and lower rates of hepatotoxicity. However, the rate of treatment-limiting adverse events was higher in the rifapentine-isoniazid regimen compared to the nine-month isoniazid regimen.

Adverse effects

Common side effects include

allergic reaction Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

elevated transaminases In medicine, the presence of elevated transaminases, commonly the transaminases alanine transaminase (ALT) and aspartate transaminase (AST), may be an indicator of liver dysfunction. Other terms include transaminasemia, and elevated liver enzym ...

, and

pyuria Pyuria is the condition of urine containing white blood cells or pus. Defined as the presence of 6-10 or more neutrophils per high power field of unspun, voided mid-stream urine, it can be a sign of a bacterial urinary tract infection. Pyuria ...

. Overdoses have been associated with

hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. "Gross hematuria" occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable with ...

and

hyperuricemia Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 ...

Pregnancy

Rifapentine in pregnant women has not been studied, but animal reproduction studies have resulted in fetal harm and were teratogenic.

Contraindications

Rifapentine should be avoided in patients with an allergy to the

class of drugs. This drug class includes

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...

and

rifabutin Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent and treat ''Mycobacterium avium'' complex. It is typically only used in those who cannot tolerate rifampin such as people with HIV/AIDS on antiretrovirals. For active tuberc ...

Interactions

Rifapentine induces metabolism by CYP3A4, CYP2C8 and CYP2C9 enzymes. It may be necessary to adjust the dosage of drugs metabolized by these enzymes if they are taken with rifapentine. Examples of drugs that may be affected by rifapentine include

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

digoxin Digoxin (better known as digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart disease, heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. ...

, protease inhibitors and

birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. It is the oral form of combined hormonal contra ...

Chemical structure

The chemical structure of rifapentine is similar to that of

, with the notable substitution of a methyl group for a

cyclopentane Cyclopentane (also called C pentane) is a highly flammable alicyclic compound, alicyclic hydrocarbon with chemical formula C5H10, C5H10 and CAS number 287-92-3, consisting of a ring of five carbon atoms each bonded with two hydrogen atoms above and ...

(C₅H₉) group.

History

Rifapentine was first synthesized in 1965, by the same company that produced

. The drug was approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) in June 1998. It is made from rifampicin. Rifapentine was granted

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designation by the FDA in June 1995, and by the European Commission in June 2010.

Society and culture

Cancer-causing impurities

In August 2020, the U.S.

(FDA) became aware of nitrosamine impurities in certain samples of rifapentine. The FDA and manufacturers are investigating the origin of these impurities in rifapentine, and the agency is developing testing methods for regulators and industry to detect the 1-cyclopentyl-4-nitrosopiperazine (CPNP). CPNP belongs to the nitrosamine class of compounds, some of which are classified as probable or possible human carcinogens (substances that could cause cancer), based on laboratory tests such as rodent carcinogenicity studies. Although there are no data available to directly evaluate the carcinogenic potential of CPNP, information available on closely related nitrosamine compounds was used to calculate lifetime exposure limits for CPNP. As of January 2021, the FDA continues to investigate the presence of 1-methyl-4-nitrosopiperazine (MNP) in rifampin or 1-cyclopentyl-4-nitrosopiperazine (CPNP) in rifapentine approved for sale in the US.

References

External links

* {{Authority control Antileprotic drugs Cyclopentanes CYP3A4 inducers Orphan drugs Rifamycin antibiotics Wikipedia medicine articles ready to translate Sanofi World Health Organization essential medicines