rifapentine

Absorption: 70% absorbed following oral administration.

Distribution: Widely distributed in body tissues and fluids.

Protein Binding: Rifapentine: 97.7%;desacetyl rifapentine: 93.2%.

Metabolism/Excretion: Mostly metabolized by the liver; 17% excreted by the kidneys; some conversion to another active compound (25-desacetyl rifapentine).

Half-Life: 13 hr (rifapentine and desacetyl rifapentine).

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	5–6 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to rifapentine or other rifamycins (rifampin or rifabutin);
Patients with HIV and active tuberculosis;
Porphyria (may worsen condition);
OB: Pregnancy (may cause fetal harm).

Use Cautiously in:

History of liver disease;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children <12 yr (safety and effectiveness not established).

Exercise Extreme Caution in:

Concurrent use of protease inhibitor.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension

Derm: acne, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), pruritus, rash, STEVENS-JOHNSON SYNDROME

EENT: red-orange discoloration of tears

GI: ↑liver enzymes, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), anorexia, diarrhea, dyspepsia, nausea, red-orange discoloration of saliva, vomiting

GU: hematuria, proteinuria, pyuria, red-orange discoloration of urine, urinary casts

Hemat: anemia, leukopenia, lymphopenia, neutropenia, thrombocytosis

MS: arthralgia

Neuro: dizziness, headache

Resp: hemoptysis

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), pain

Interactions ⬆ ⬇

Drug-drug:

↑metabolism and may ↓ levels of phenytoin, disopyramide, mexiletine, quinidine, chloramphenicol, clarithromycin, dapsone, doxycycline, fluoroquinolones, warfarin, fluconazole, itraconazole, ketoconazole, some sedative/hypnotics (benzodiazepines and barbiturates), some beta blockers, some calcium channel blockers, corticosteroids, digoxin, hormonal contraceptives, haloperidol, protease inhibitors (ritonavir, nelfinavir), sulfonylurea oral hypoglycemic agents, cyclosporine, tacrolimus, levothyroxine, some opioids, progestins, quinine, sildenafil, theophylline, some reverse transcriptase inhibitors, and tricyclic antidepressants; dosage adjustments may be necessary.
Antacids↓ absorption.

Drug-Food:

Food ↑ absorption.

Route/Dosage ⬆ ⬇

Must be used in combination with other antituberculars

Tuberculosis

PO (Adults ): Intensive phase: 600 mg twice weekly (not less than 72 hr between doses) for 2 mo as directly observed therapy;Continuation phase: 600 mg once weekly for 4 mo.

Latent Tuberculosis

PO (Adults and Children ≥2 yr and >50 kg): 900 mg once weekly for 12 wk.
PO (Adults and Children ≥2 yr and >32.1–50 kg): 750 mg once weekly for 12 wk.
PO (Adults and Children ≥2 yr and >25.1–32 kg): 600 mg once weekly for 12 wk.
PO (Adults and Children ≥2 yr and >14.1–25 kg): 450 mg once weekly for 12 wk.
PO (Adults and Children ≥2 yr and >10–14 kg): 300 mg once weekly for 12 wk.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Perform mycobacterial studies and susceptibility tests prior to and periodically during therapy to detect possible resistance.
Assess lung sounds and character and amount of sputum periodically throughout therapy.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of Clostridioides difficile-associated diarrhea (CDAD). May begin up to several wk following cessation of therapy.
Monitor for signs and symptoms of skin reactions (skin rash, mucosal lesions). May lead to Stevens-Johnson syndrome or DRESS.

Lab Test Considerations:

Assess hepatic enzymes, bilirubin, CBC, and platelet count prior to therapy. Monitor at least monthly, especially in relation to adverse reactions. Patients with liver disease or abnormal liver tests should have liver tests (especially AST and ALT) monitored every 2–4 weeks. Signs of worsening disease may require discontinuation.
- May interfere with methods for determining serum folate and vitamin B levels and with urine tests based on color reaction.
- Hyperuricemia is common during intensive phase, especially when combined with pyrazinamide.

Implementation ⬆ ⬇

Do not confuse rifapentine with rifabutin.
Rifapentine is not administered alone. When used with isoniazid, pyridoxine (vitamin B) is administered concurrently in patients who are malnourished, predisposed to neuropathy (patients with alcoholism or diabetes), or adolescents to prevent neuropathy.
PO: May be administered with food to minimize nausea, vomiting, or GI upset and increase bioavailability. If unable to swallow, tablets can be crushed and placed in small amount of semi-solid food.
- Antacids should not be administered within 1 hr before or 2 hr after rifapentine.

Patient/Family Teaching ⬆ ⬇

Advise patient to take medication as directed; not to skip doses or double up on missed doses of daily companion medications. Emphasize the importance of continuing therapy even after symptoms have subsided. Length of therapy for tuberculosis depends on regimen being used and underlying disease states.
Advise patient to notify health care professional promptly if fever, malaise, darkened urine, yellow eyes and skin, nausea, vomiting, anorexia, or pain or swelling of joints occur.
Instruct patient to notify health care professional signs and symptoms of severe skin reactions (rash, peeling or bleeding skin, swollen face, lips, mouth tongue or throat, sores or blisters on the inside of mouth or lips, flu-like symptoms, red and painful skin) or if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
Caution patient to avoid the use of alcohol during this therapy; may increase the risk of hepatotoxicity.
Rifapentine may occasionally cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Inform patient that saliva, sputum, teeth, tongue, sweat, tears, CSF, urine, and feces may become red-orange, and that soft contact lenses may become permanently discolored.
Rep: Advise patient that rifepentine is teratogenic and may decrease the effectiveness of oral contraceptives. Counsel patient to use a nonhormonal form of contraception during therapy and to avoid breastfeeding. Monitor infants exposed to rifapentine through breast milk for signs of hepatotoxicity (irritability, prolonged unexplained crying, yellowing of the eyes, loss of appetite, vomiting, darkening of the urine, pale stool).
Emphasize the importance of regular follow-up exams to monitor progress and to check for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇