Rifapentine

Pronunciation: (Riff-ah-pen-teen)
Class: Antituberculosis agent

Trade Names

Priftin
- Tablets 150 mg

Pharmacology

Inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis . Bactericidal for intracellular and extracellular M. tuberculosis organisms.

Pharmacokinetics

Absorption

Rapid and well absorbed. Absolute bioavailability is not determined. Relative bioavailability is 70% (oral solution). T _max is 5 to 6 h (rifapentine); 11.25 h (metabolite). C _max is 15.05 mcg/mL (rifapentine); 6.26 mcg/mL (25-desacetyl rifapentine metabolite). Food increased AUC and C _max . Steady state is 10 days.

Distribution

Vd is 70 L. Protein binding is 97.7% (rifapentine) and 93.2% (25-desacetyl rifapentine metabolite). Both bound mainly to albumin.

Metabolism

Hepatic; rifapentine undergoes enzymatic transformation to active 25-desacetyl rifapentine.

Elimination

Eliminated in urine (17%) and feces (70%).

Indications and Usage

Treatment of pulmonary tuberculosis in conjunction with 1 or more other antituberculosis drugs to which the isolate is susceptible.

Contraindications

Hypersensitivity to any of the rifamycins (rifabutin, rifampin).

Dosage and Administration

Adults and children (12 yr of age or older)

PO Intensive phase: 600 mg twice weekly (with an interval of 3 days or more) for 2 mo. Continuation phase: 600 mg once weekly for 4 mo.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F). Protect from excessive heat and humidity.

Drug Interactions

Amitriptyline, amprenavir, azole antifungal agents, barbiturates, buspirone, chloramphenicol, clarithromycin, clofibrate, clozapine, corticosteroids, cyclosporine, dapsone, delavirdine, diazepam, diltiazem, digitalis glycosides, disopyramide, doxycycline, erythromycin, fluconazole, fluoroquinolones, haloperidol, indinavir, itraconazole, ketoconazole, levothyroxine, losartan, methadone, mexiletine, morphine, nelfinavir, nifedipine, nortriptyline, ondansetron, oral contraceptives, phenytoin, progestins, quinidine, quinine, ritonavir, saquinavir, sildenafil, sulfonylureas, tacrolimus, tamoxifen, theophylline, tocainide, toremifene, tricyclic antidepressants, troleandomycin, verapamil, warfarin, zidovudine, zolpidem

Has same interaction potential as rifampin. Potent inducer of hepatic drug metabolizing enzymes. Reduced levels and efficacy of target drugs may occur.

Ketoconazole

May reduce rifapentine plasma levels, decreasing the therapeutic effects.

Laboratory Test Interactions

May alter microbiological assays for folate and vitamin B ₁₂ .

Adverse Reactions

The following adverse reactions were reported in patients receiving rifapentine combination therapy and occurred in at least 1% of the patients.

Cardiovascular

Hypertension.

CNS

Headache; dizziness.

Dermatologic

Rash; acne; pruritus; maculopapular rash.

GI

Anorexia; nausea; vomiting; dyspepsia; diarrhea; hemoptysis.

Genitourinary

Pyuria; proteinuria; hematuria; urinary casts.

Hematologic

Neutropenia; lymphopenia; anemia; leukopenia; thrombocytosis.

Hepatic

Increased AST and ALT; hepatitis.

Miscellaneous

Arthralgia; pain; hyperuricemia.

Precautions

Monitor

Conduct baseline measurements of hepatic enzymes, bilirubin, CBC, and platelet counts. Question patients monthly concerning symptoms of adverse reactions. Follow up on abnormalities, including laboratory tests.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 12 yr of age.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Hepatic Function

Use with caution under strict medical supervision.

Body fluids

May produce a reddish-orange discoloration of the feces, urine, saliva, sweat, sputum, tears, and other body fluids. Contact lenses or dentures may become permanently discolored.

Hyperbilirubinemia

May occur from competition for excretory pathways between rifapentine and bilirubin.

Porphyria

Do not use in patients with porphyria.

Pseudomembranous colitis

Should be considered in patients in whom diarrhea develops.

Overdosage

Symptoms

Headache, urinary frequency, heartburn, transient elevations of hepatic enzymes.

Patient Information

Review dosing schedule and prescribed length of therapy with patient.
Ensure patient understands treatment will be lengthy and the entire course of treatment, including companion drugs, must be completed to avoid relapse or development of resistance. Emphasize the importance of not missing any doses of any tuberculosis medications.
Advise patient to take each dose without regard to meals but to take with food if stomach upset occurs.
Advise patient that rifapentine may produce a red/orange discoloration of body tissues and fluids (eg, skin, teeth, tongue, urine, feces, saliva, sputum, tears, sweat, breast milk). Caution patient that contact lenses or dentures may be permanently stained.
Advise patient to contact health care provider immediately of any of the following: fever; general body discomfort; persistent nausea or vomiting; dark urine; yellowing of skin or eyes; pain or swelling of the joints.
Warn patient that diarrhea containing blood or pus may be a sign of a serious disorder and to seek medical care if noted and not treat at home.
Caution women using oral or parenteral hormonal contraception that rifapentine will reduce the effectiveness of contraceptive and to change to nonhormonal methods of contraception (eg, condoms, diaphragm) to prevent pregnancy.