Priftin
Priftin - General Information
Priftin is an antibiotic drug used in the treatment of tuberculosis. It inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme.
Pharmacology of Priftin
Priftin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.
Priftin for patients
Priftin Interactions
Rigapentine-Indinavir Interaction: In a study in which 600 mg rifapentine was administered twice weekly for 14 days followed by rifapentine twice weekly plus 800 mg indinavir 3 times a day for an additional 14 days, indinavir Cmax decreased by 55% while AUC reduced by 70%. Clearance of indinavir increased by 3-fold in the presence of rifapentine while half-life did not change. But when indinavir was administrated for 14 days followed by coadministration with rifapentine for an additional 14 days, indinavir did not affect the pharmacokinetics of rifapentine. Rifapentine should be used with extreme caution, if at all, in patients who are also taking protease inhibitors.
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 enzymes 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 600mg 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 following drugs or of drugs metabolized by cytochrome P4503A4 or P4502C8/9 may be necessary if they are given concurrently with rifapentine. Patients using oral or other systemic hormonal contraceptives should be advised to change to nonhormonal methods of birth control.
Anticonvulsants: e.g., phenytoin
Antiarrhythmics: e.g., disopyramide, mexiletine. Quinidine, tocainide
Antibiotics: e.g., : chloramphenicol, clarithromycin, dapsone. Doxycycline, fluoroquinolones (such as ciprofloxacin)
Oral anticoagulants: e.g., warfarin
Antifungals:e.g., fluconazole, Itraconazole, ketoconazole
Barbiturates
Beta-blockers, calcium channel blockers: e.g., diltiazem, nifedipine, verapamil
Corticosteroids:
Cardiac glycoside preparations
Clofibrate:
Oral or other systemic hormonal contraceptives
Haloperidol
HIV protease inhibitors: e.g., indinavir, ritonavir, sequinavir
Oral hypoglycemic agents: e.g., sulfonylureas
Immunosuppressants: e.g., cyclosporine, tacrolimus
Levothyroxine
Narcotic analgesics: e.g., methadone
Progestins
Quinine
Reverse transcriptase inhibitors:e.g., delavirdine, zidovudine
Sildenafil
Theophylline
Tricyclic antidepressants: e.g., amtoptyline, nortriptyline.
The conversion of rifapentine to 25-desacetyl rifapentine is mediated by an esterase enzyme. There is minimal potential for rifapentine metabolism to be inhibited or induced by another drug, or for rifapentine to inhibit the metabolism of another drug based upon the characteristics of the esterase enzymes. Rifapentine does not induce its own metabolism. Since rifapentine is highly bound to albumin, drug displacement interactions may also occur.
In Clinical Study 008 patients were advised to take rifapentine at least 1 hour before or 2 hours after the ingestion of antacids.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, studies with rifapentine have not been completed. Rifapentine was negative in the following genotoxicity tests: in vitro gene routation assay in bacteria (Ames test); in vitro point mutation test in Aspergillus nidulans; in vitro gene conversion assay in saccharomyces cerevisiae; host-mediated (mouse) gene conversion assay with saccharomyces cerevisiae; in vitro Chinese hamster ovary cell/hypoxanthine-guanine-phosphoribosyl transferase (CHO/HGPRT), forward mutation assay: in vitro chromosomal aberration assay utilizing rat lymphocytes; and in vivo mouse bone marrow mocronucleus assay. Fertility and reproductive performance were not affected by oral administration of rifapentine to male and female rats at doses of up to one-third of the human dose (based on body surface area conversions).
Pregnancy Category C
Teratogenic Effects
Rifapentine has been shown to be teratogenic in rats and rabbits. In rats, when given in doses 0.6 times the human dose (based on body surface area comparisons )during the period if organogenesis, pups showed cleft palates, right aortic arch and increased incidence if delayed ossification and increased number of ribs. Rabbits treated with drug at doses between 0.3 and 1.3 times the human dose (based on body surface area comparison) displayed major malformations including ovarian agenesis, pes varus, arhinia, microphthalmia and irregularities of the ossified facial tissues (4 of 321 examined fetuses).
Nonteratogenic Effects
In rats, rifapentine administration was associated with increased resorption rate and post implantation loss, decreased mean fetus weight, increased number of stillborn pups and slightly increased mortality during lactation. Rabbits given 1.3 times the human dose (based on body surface area comparisons) showed higher post-implantation losses and an increased incidence of stillborn pups.
When rifapentine was administered at 0.3 times the human dose (based on body surface area comparisons) to mated female rats late in gestation (from day 15 of gestation to day 21 postpartum), pup weights and gestational survival (live pups born/pups born) were reduced compared to controls.
Pregnancy - Human Experience
There are no adequate and well-controlled studies in pregnant women. In Clinical Study 008, six patients randomized to rifapentine became pregnant; two had normal deliveries, two had first trimester spontaneous abortions one had an elective abortion and one patient was lost to follow-up Of the two patients who spontaneously aborted, co-morbid conditions of ethanol abuse in one and HIV infection in the other were noted.
When administered during the last few weeks of pregnancy, rifampin can cause postnatal hemorrhages in the mother and infant for which treatment with Vitamin K may be indicated, Thus, patients and infants who receive rifapentine during the last few weeks of pregnancy should have appropriate clothing parameters evaluated.
Rifapentine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether rifapentine is excreated in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
The safety and effectiveness of rifapentine in pediatric patients under the age of 12 have not been established. A pharmacokinetic study was conducted in 12 to 15 year old healthy volunteers.
Priftin Contraindications
This product is contraindicated in patients with a history of hypersensitivity to any of the rifamycin (e.g., rifampin and rifabutin).
Additional information about Priftin
Priftin Indication: For the treatment of pulmonary tuberculosis.
Mechanism Of Action: Priftin has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages. Priftin inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. Priftin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Rifapentine
Synonyms: Cyclopentyl rifampin
Drug Category: Antimycobacterials; Antibiotics, Antitubercular; Leprostatic Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Rifapentine: Priftin;
Absorption: Rapidly and well absorbed from the gastrointestinal tract.
Toxicity (Overdose): Not Available
Protein Binding: 97.7% (bound to plasma proteins)
Biotransformation: Hepatic
Half Life: Not Available
Dosage Forms of Priftin: Tablet Oral
Chemical IUPAC Name: Not Available
Chemical Formula: C47H64N4O12
Rifapentine on Wikipedia: https://en.wikipedia.org/wiki/Rifapentine
Organisms Affected: Mycobacterium
